ANNEXURE I TERMS OF REFERENCE - …environmentclearance.nic.in/writereaddata/FormB/TOR/Additional... · M/s. PRANSHAV HEALTH CARE, JHAGADIA, BHARUCH Jyoti Om Chemical Research Centre

M/s. PRANSHAV HEALTH CARE, JHAGADIA, BHARUCH

Jyoti Om Chemical Research Centre Pvt. Ltd.

1

ANNEXURE I

TERMS OF REFERENCE

• Site description and plant lay out.

• List of raw materials and consumption quantity.

• List of finished products and production quantity.

• Manufacturing process details with mass balance.

• Details of flue gas emission, process emissions, waste water discharge & solid

wastegeneration and disposal.

• Complete water balance.

• Details of Effluent Treatment plant.

• Details of air pollution control systems.

• One season base line data of soil, water, air and noise for study area.

• Environment impact assessment due to excavation and constructionactivities,

manufacturing process and its operations etc.

• Details of Environmental Management Plan (EMP) and mitigationmeasures.

• Occupational health and safety program for the project.

• TOR prescribed by MoEF for this sector will be taken in to account.



2

ANNEXURE II

LIST OF PARTNERS

Name of Partners Address

1. Mr. Jignesh Sureshbhai Patel 2, Sukhshanti Society-2, Near Gattuchowkdi,

GIDC, Ankleshwar-393002

Mob. No.- 9824206088

2. Mr. Ankit Sureshbhai Patel 2, Sukhshanti Society-2, Near Gattuchowkdi,


Mob. No.- 9824140088

3. Mrs. Manjulaben Sureshbhai

Patel

2, Sukhshanti Society-2, Near Gattuchowkdi,


Mob. No.- 9824140088



3

ANNEXURE III A

SITE PLAN



4

ANNEXURE III B

PLANT LAYOUT



5

ANNEXURE IV

LIST OF EXISTING PRODUCTS (As per CTE No. 70101)

Sr. No. Product Name Quantity (MT/M)

1 Potassium Chloride 500

(either individual of total 7

product)

2 Potassium fluoride

3 Potassium Bromide

4 Potassium sulphate

5 Calcium sulphate

6 Magnesium sulphate

7 Sodium Bromide

8 Manganese Sulphate 27% solution 50

LIST OF PROPOSED PRODUCTS

Sr. No. Product Name Quantity

(MT/M)

Group A Individual Product

1 Atorvastatin calcium 20.00

2 CH base (Product) 50.00

3 Pentaprazol Sodium 30.00

4 Tertiary Butyl Hydroquinon 40.00

Group B Pharmaceutical Drug 20

PROTON PUMP INHIBITOR (REDUCTION OF

GASTRIC ACID/ ANTACID)

5 Esomeprazole Magnesium Dihydrate

6 Dexlansoprazole

OCULAR CARBONIC ANHYDRASE INHIBITOR(FOR

OPEN ANGLE GLAUCOMA

7 Brinzolamide

8 Dorzolamide HCl

ANTI-DIABETIC DRUGS

9 Canagliflogin

10 Dapagliflozin

11 Vildagliptin



6

CHEMOTHERAPEUTIC DRUG

12 Capecitabine

ANTIBIOTIC (3RD

GENERATION CEPHALOSPORIN)

13 Cefsulodine Sodium

ANTICOAGULANTS

14 Dabigetran

15 Rivaroxaban

FOR TREATMENT OF PREMATURE EJACULATION

16 Dapoxetine Hydrochloride

FOR TREATMENT OF HIV INFECTION

17 Darunavir

ANTHRAQUINONE (FOR TREATMENT OF

OSTEOARTHRITIS)

18 Diacerein

ANTI-HYPERTENSIVE DRUGS

19 Irbesartan

20 Telmisartan

21 Cilnipine

22 NEBIVOLOL HCL

LEUKOTRIENE ANTAGONIST (FOR TREATMENT

OF BRONCHIAL ASTHMA)

23 Montelukast Sodium

ANTI-FUNGAL DRUGS

24 Posaconazole

ATYPICAL ANTI-PSYCHOTIC (FOR TREATMENT

OF SCHIZOPHRENIA)

25 Quetiapine Hemifumarate

PREVENT OSTEOPOROSIS

26 Risedronate Sodium

ANTIDEPRESSANT DRUGS

27 Vilazodone HCl

28 Agomealtine

ANTI-PSYCHOTIC DRUG

29 Levosulpiride

FOR TREATMENT OF BENIGN PROSTATIC

HYPERPLASIA

30 Tamsulosin HCl

ANTI-EPILEPTIC DRUGS

31 Carbamazepine

32 Levetiracetam



7

ANTIMUSCARINIC DRUG (FOR TREATMENT OF

OVERACTIVE BLADDER SYNDROME)

33 Fesoterodine

HYPERTENSION

34 Bosentan Monohydrate

FOR TREATMENT OF GOUT

35 Febuxostat

Group C Paraben 50

36 Methyl Paraben

37 Ethyl Paraben

38 Propyl Paraben

39 Butyl Paraben

40 Iso Propyl Paraben

Group d Intermediate 40

41 4- Amino Pyridine

42 Dimethyl Ameno Propiophenone

43 Guaicol

45 Veratrole

46 Diethyl Ethyl Melonate

47 3,5 Dinitrobenzoic acid

48 P - Hydroxy Aceto Phenone

49 2-Mercaptobenzimidazole

50 Bronopol (BP)

51 2 Mercapto 5 Methoxy Benzimimidazone

52 3,5 Dibenzyloxy Acetophenone

53 1(2,3 Dichloro Phenyl) Piperazine

54 1h,1,2,4 Triazole

55 Acebrophylline

56 Lasamide

57 Methyl Nicotinate

58 Fingolimod HCL

59 Cetyl Pyridinium Chloride

60 Ambroxol Hydrochloride

61 1 (2,4 Dichloro Phynyl) 2 (1- Imidazoleylethanol

62 Furoic Acid

Group E Fine Chemicals 200

63 Methyl Acetate

64 Ethyl Acetate

Total 450



8

TABLE: 1

LIST OF BY-PRODUCTS

Sr. No. Product Name Quantity (MT/M)

1 Acetic acid 2.56

2 Sodium L (+) Mandelate 9.429

3 Propanoic acid 14.76

4 Trityl chloride 13.014

5 Methane Sulfonic acid 3.156

6 Potassium Bromide 8.139



9

ANNEXURE V

EXISTING PRODUCT’S RAW MATERIAL CONSUMPTION QUANTITY (As

per CTE No. 70101)

Sr.

No.

Product Quantity

(MT/MT)

Raw Material Quantity

(MT/MT)

1 Potassium Chloride 500

(either

individual

of total 7

product)

Potassium hydroxide 662.50

Hydrochloric Acid 759.50

Total 1422.00

2 Potassium fluoride Potassium hydroxide 867.50

Hydrofloric Acid 352.00

Total 1219.50

3 Potassium Bromide Potassium hydroxide 420.50

Hydrobromic Acid 709.50

Total 1130.00

4 Potassium sulphate Potassium hydroxide 575.00

Sulphuric Acid 402.00

Total 977.00

5 Calcium sulphate Calcium carbonate 367.50


Total 887.00

6 Magnesium

sulphate

Magnesium oxide 166.50


Total 983.50

7 Sodium Bromide Sodium hydroxide 396.00

Hydrobromic Acid 818.50

Total 1214.50

8 Manganese Sulphate

27% solution

50 Manganese oxide 4.30


Total 50.65

PROPOSED PRODUCT’S RAW MATERIAL CONSUMPTION QUANTITY

Sr.

No.

Product Quantity

(MT/MT)

Raw Material Quantity

(MT/MT)

1 Atorvastatin

calcium

20 1,1-Dimethyl Ethyl -6-(2-

Aminoethyl) 15.39

4-Fluoro -2-Methyl-1-

Oxopropyl 23.52

Cyclohexane 60.00

Iso Propyl Alcohol(IPA) 50.01


Acetonitrile 70.00

Sodium Hydroxide 2.92

Calcium Acetate 3.58



10

Hyflow 0.24

TOTAL 227.06

2 CH Base 50 Hexa Methyl Di Amine 337.00

Sodium Di Cynamide 517.00

N Butanol 1008.00

Water 965.00

Tri Ethyl Amine 25.00

Sodium Hydroxide Flakes 150.00

Pca Hcl 925.00

Methanol 15.00

TOTAL 3942.00

3 Pentaprazol Sodium

30 2-Chloro 2,3 Dimethoxy

Pyridine 34.69

5-Dithiomethoxymenzimidazole 33.28

NaOH 191.63

Methenol 192.66

DCM 1245.00

TEBA 0.52

Sodium Hypochlorite 147.19

Sodium Thiosulphate Soln. 61.88

MDC 147.19

Acetic Acid 28.59

IPE 486.09

Ethyl Acetate 301.41

Charcoal 0.94

TOTAL 2871.05

4 Tertiary Butyl

Hydroquinone

40 Phosphoric Acid 2.40

Toluene 2.00

Hydroquinone 27.20

Tertiary Butanol (TBA) 18.40

TOTAL 50.00

5 Brinzolamide

4(S)-4-hydroxy-6-sulfonamide

dioxide 52.20

Methane sulfonic anhydride 12.00

Ethyl amine 6.60

Aq.Ammonia 3.99

Con.HCl 2.01

Sodium hydroxide 2.19

Pyridine 3.99

Tetra Hydrofuran(THF) 201.00

Isopropyl alcohol(IPA) 219.00

Sodium bicarbonate 2.01

Carbon 2.01

Hyflow 2.01

TOTAL 509.00

6 Canagliflogin

2-(5-bromo-2-methyl benzul)-5-

(4-flurophenyl)thiophene 42.47



11

Silyl D-gloconolactone 55.40

Methanol 333.33

Acetone 500.00

Potassium carbonate 6.67

TOTAL 937.86

7 Capecitabine

2,3-Di-O-Acetyl-5-Deoxy-5-

Fluorocytidine 24.94

n-Pentyl Chloroformate 11.40


Sodium Bicarbonate 1.00

Hydrochloric acid 1.46

Methylene Chloride(MDC) 80.00

Methanol 50.00


Activated Carbon 1.00

TOTAL 288.10

8 Cefsulodine Sodium

RS-A-Sulfophenyl Acetic Acid 10.29

(S) –A- Methyl Benzyl Amine 5.77

Acetonitrile 123.00

1-Hydroxy Benzotriazole 6.17

Methane Sulphonyl Chloride 5.23


Methylene Dichloride(MDC) 102.50

Hexane 194.50


7-Amino Cephalosporic Acid 11.96

Boron Trifluride Etherate 37.50

Tert-Butyl Acetate 5.10

Sodium Carbonate 1.00

Hyflow 1.50

Zinc Chloride 0.50

Triethyl Amine 0.50

Ethyl Acetate 20.50

Di Isopropyl Ether(Diipe) 10.00

Pyridine-4-Carboxamide 4.83

Sodium Iodide 4.00

Dimethyl Formamine 5.52

Ethanol 5.00

Sodium Acetate 3.10

Hydrochloride 0.50

Carbon 10.00

TOTAL 613.53

9 Dabigetran

3-[(1-Methyl-2-{[4-(5-oxo-4,5-

dihydro-[1,2,4]oxadiazol-3-yl)-

phenylamino]-methyl)-

1Hbenzoimidazole-5-carbonyl)-

pyridin-2-yl amino]- 19.40



12

propionic acidethyl ester

P-toluene sulphonic acid 5.00

Acetic acid 4.00

Ethanol 500.00

Hexa chlorofomate 5.60

Acetone 240.00

Potassium Hydroxide 1.92

Hydrochloric acid 0.08

TOTAL 776.00

10 Dapoxetine

Hydrochloride

�-(Dimethylamino)

Benzenepropanol 21.25

1-Fluoronaphthalene 17.30



Dimethyl Sulfoxide(DMSO) 250.00

n-Propanol 200.00

Activated carbon 5.00

TOTAL 508.20

11 Darunavir

(3R,3as,4ar)-

Hexahydrofuro[2,3-B]Furan-3-

Ol 9.51

4-Amino-N-(2R,3S)(3-Amino-

2-Hydroxy-4-Phenyl-Butyl)-N-

Isobutyl Benzenesulfonamide 28.59

Disucinimidyl Carbonate 18.72

Sulphuric Acid 0.20

2-Methyl2-Butanol 1.20

Methylene Chloride(MDC) 60.00

Cyclohexane 48.00


Sodium Chloride 0.20

Sodium Sulphate 0.20



Total 167.57

12 Dexlansoprazole

2-[3-Methyl-4-(2,2,2-Trifluoro-

Ethoxy)-Pyridin-2-

Ylmethanesulfinyl]-1H-

Benzoimidazole

29.41

L (+) Mandelic Acid 12.12


Diethyl Tartarate 20.00

Titanium Isopropoxide 6.00

Triethyl Amine 4.00

Acetone 120.00

Dichloromethane(MDC) 80.40




13

TOTAL 282.35

13 Diacerein

Aloe Emodine 39.32

Sodium Dichromate Dihydrate 43.36



Tetrahydrofuran(THF) 800.00

Acetone 220.00

Propionic Anhydride 35.20

Conc.HCl 7.28

Toluene 44.00

Acetic Anhydride 20.36

N-Methyl Pyrrolidone 69.97

Methanol 44.00


Celite 4.00

Total 1361.82

14 Dorzolamide HCl

(±)-Trans-5,6-Dihydro-4H-4-

Ethyl Amino-6-

Methylthieno[2,3-B]Thiopyran-

2-Sulfonamide-7,7-Dioxide

59.80


N-Butanol 464.00

Methanol 604.00


Acetone 16.00

(-)Di-Para-Toluoyl-Ltartaric

Acid Monohydrate

20.00





Total 1537.68

15 Dapagliflozin

Intermediate-I 17.40

Intermediate-II 24.93

N-Butyl Lithium In THF 4.73

Toluene 86.67

Acetonitrile 33.33

Methylene Dichloride(MDC) 86.67

Triethyl Tin Hydride 0.33

Trifluro Borate-Etharate 0.67

Total 254.73

16 Esomeprazole

Magnesium

5-Methoxy-2-[[(4-methoxy-3,5-

dimethylpyridin-2-

yl)methyl]thio]-1H-

benzimidazole 48.06

Hydrogen Peroxide 4.97

Vanadium acetyl acetonate 0.14



14

Sodium hydroxide 2.94

Acetone 224.00

Methanol 90.00

Acetic acid 1.20

Ammonia liquor 0.60

Magnesium Chloride 4.70

Methylenechloride(MDC) 160.00

Toluene 100.00

(S)-(-)-1,1-Bi-2-Naphthol 0.40

TOTAL 637.01

17 Irbesartan

2-Butyl-1,3-

Diazaspiro[4,4]Non-1-Ene-4-

One Hydrochloride 23.17

5-[4'-(Bromomethyl) Biphenyl-

2-Yl]-1-Trityl-1Htetrazole 55.99

Methanolic HCl 6.89

Ethylacetate 100.00

Methanol 133.33

Toluene 100.00

Methylene Methylene 113.33

Isopropanol(IPA) 120.00

Acetone 100.00

30% Sodiumhydroxide Lye 26.07

Sulfuric Acid 5.00


Total 784.43

18 Montelukast

Sodium

2-[2-[3(S)-[3-[2-(7-Chloro-2-

Quinolinyl)-Ethenyl]Phenyl]-3-

Hydroxypropyl]Phenyl-2-

Propanol

26.53

2-[1-(Sulfonyl

Methyl)Cyclopropyl]Acetic

Acid

8.46

Methane Sulfonyl Chloride 6.63


N,N-Diisopropylethylamine 0.13



Acetic Acid 0.26

Toluene 20.00

Acetonitrile 17.33

Methanol 26.67

N-Hexane 34.67


Total 145.63

19

Posaconazole

N-{4-[4-(4-Hydroxyphenyl)-

Piperazin-1-Yl]-Phenyl}- 12.06



15

Carbamic Acid Phenyl Ester

Formic Acid N'-(2-Benzyloxy-1-

Ethyl-Propyl)-Hydrazide 7.32

(5R-Cis)-5-(2,4-

Difluorophenyl)-5-(1,2,4-

Triazol-1-

Ylmethyl)Tetrahydrofuran-3-

Methanol Tosylate 13.96

Methanol Tosylate 1.24

2,3,4,6,7,8,9,10-Octahydro

Pyrimido[1,2-A]Azepine 1.50

Tetrahydrofuran(THF) 35.00

Formic Acid 50.00

Dimethyl Sulfoxide 90.00

Palladium 1.00



Total 2213.67

20 Quetiapine

Hemifumarate

Dibenzo-(1,4)-Thiazepine-

11(10H)-One 31.48

2-(2-(Piperazin-1-

Yl)Ethoxy)Ethanol 24.13

Fumaric Acid 8.04

Thionyl Chloride 1.00




Toluene 140.00

Ethanol 170.00


Total 382.61

21 Risedronate Sodium

3- Pyridyl Acetic Acid 22.27

3- Pyridyl Acetic Acid 26.64

Diethyl Carbonate 15.00

Caustic Soda Lye 1.00

Sodium Hydroxide Flakes 6.17

Phosphorous Trichloride 0.50

Methane Sulfonic Acid 10.00

Isopropyl Alcohol 116.00


Hyflow 1.00


Total 203.98

22 Telmisartan

1H-Benzimidazole-2npropyl-4-

Methyl-6-(1-Methyl

Benzimidazole-2yl] 23.13

4-Methyl-(Bromomethyl) Bi 23.18



16

Phenyl Carboxylate

Potassium Hydroxide 4.26

Methyl Iso Butyl Ketone

(MIBK) 83.20



Acetic Acid 29.87

Methanol 60.93

Charcoal Activated Carbon 0.27

Total 225.95

23 Vilazodone HCl

5-{4-[4-(5-Cyano-1H-Indol-3-

Yl)-Butyl]-Piperazin-1-Yl}-

Benzofuran-2-Carboxylicacid

Methyl Ester 48.20

Ammonia 1.04

Methanol 522.00


Sodium Hydroxide 30% 2.44

Isopopyl Alcohol(IPA) 240.00


Total 819.87

24 Levosulpiride

Mono Ethylene Glycol 20.00

2-Methoxy-5-Sulphomyl Methyl

Benzoate 15.00

S-1-Ethyl-5-Aminomethyl

Pyrollidine 7.80

Total 42.80

25

Cilnidipine

Toluene 20.00

2-Methoxy-Ethyl-(3-Nitro

Benzylidine)Acetoacetate 14.00

3-Amino Crotonic Acid

Cinnamyl Ester 10.00

Total 44.00

26 NEBIVOLOL HCL

Benzo Pyran Acetaldehyde 166.67

Benzo Pyran Ethelamine 55.56

Sodium Cyano Borohydried 19.44

THF 3611.11

Methenol 1944.44

Sodium bicarbonate 561.11


6N HCl 277.78

2N HCl 111.94

diethyl Ether 111.11

TOTAL 7970.27

27 Tamsulosin HCl Dimethylformamide 206.86

Ethoxy Phenoxy Ethyl Bromide 21.90

(R)-(-)[2-Aminopropyl]-2- 32.95



17

Methoxy Benzene Sulfonamide

Methylene Chloride 1366.86

Ammonia Liquor 100.95

Isopropyl Alcohol 978.29

Isopropyl Alcohol (Wash) 495.81

IPA 43.81

HCl 43.81

Water+IPA (7+12.5) (wash) 111.42

IPA 26.67

IPA+HCl (14+13.6) 25.90


TOTAL 3456.38

28 Carbamazepine Methanol 20.28

Iminostilbenecarbonyl Chloride 25.64

Ammonia Liquor 56.15

Toluene 0.80

NaOH 0.57

Acetone 101.30

Hyflo 0.25


Acetone (wash) 28.78

Total 234.03

29 FESOTERODINE Benzyl Amine DPTT 109.08


Cerric Ammonium Nitrate 250.88

NaBH4 15.48

Fumic Acid 29.54

Hydrogen Gas 0.26

Isobutyryl Chloride 6.80

Triethylamine 6.02

TOTAL 532.58

30 Bosentan

Monohydrate

4,6‐Dichloro‐5‐(2‐Methoxyphen

oxy)‐2,2‐Bipysimidine 14.52

4‐Tert‐Butylbenzene

Sulfonamide 8.86


Potassium Carbonate 24.12

Sodium Tert Butoxide 19.96

Ethylene Glycol 246.78

TOTAL 317.82

31 VILDAGLIPTIN

DMF 108.00

KSM-II 14.40

KSM-I 15.40

Pottasium Carbonate 62.20

Isopropyl Acetate 100.80

Dichromomethane 425.00

Potassium Hydrogen Sulfate 75.00



18

NaCl 13.40

Charcoal 1.00

Acetone 264.60

Total 1079.80

32 RIVAROXABAN

(4‐4‐Aminophenyl)‐Morpholin‐3

‐One 28.22

Glycidyl Phthalimide 32.74

4‐Dimethylaminopyridine(DMA

P) 0.14

Cdi 80.68

5‐Chlorothiophene‐2‐Cacoxylic

Acid 24.60

Sodium Acetate 29.60

Oxalyl Chloride 29.90

Aq. Methyl Amine 32.54


Total 271.96

33 FEBUXOSTAT

Ksm 30.94

Isobutyl Bromide 23.24

Potassium Carbonate 36.68

Ammonium Hydroxide. Hcl 6.46




Acetone 15.00

Total 130.32

34 AGOMEALTINE

2‐(7‐Methoxy‐1‐Napthyl)Aceton

itrile/ Agomelatine 22.47

Hydrogen Gas 0.45

Isopropyl Alcohal HCl 16.63

Sodium Acetate Anhydrous 9.44

Acetic Anhydrous 11.46

TOTAL 60.45

35 Levetiracetam

DCM 775.00

Sodium Sulphate 57.60

TBAB 1.20

S(+)-2 amino butyramide

hydrochloride 23.00

4-Chloro Butyryl Chloride 28.80

KOH 51.60

Activated Charcoal 5.20

Hyflo 60.00


Acetic Acid 14.00

TOTAL 1339.60

36 Methyl Paraben

50 PHBA 50.00

Methanol 14.53



37 Propyl Paraben

38 Ethyl paraben

39 Butyl Paraben

40 Iso Propyl Paraben

41 4- Amino Pyridine

42 Dimethyl Ameno

Propiophenone

43 Guaicol

44 Veratrole

45 Diethyl Ethyl

Melonate



Sodium Bi Carb Soln (5%)

TOTAL

PHBA

Propanol

Sodium Bi Carb Soln (5%)

TOTAL

PHBA

Ethanol

Sodium Bicarb Soln (5%)

TOTAL

PHBA

Butanol


TOTAL

PHBA

Iso Propanol


TOTAL

40 NaOH

Bromine

ISO Nicotinamide

Methanol

Total

Fresh IPA

Recovered IPA

Paraformaldehyde

DMA Hcl

Acetophenone

TOTAL

Sodium carbonate

Fresh Toluene

Recovered Toluene

Catechol

DMS

HCl

TOTAL

NaOH

Fresh Toluene

Recovered Toluene

Catechol

DMS

HCl

TOTAL

Fresh Alcohol

Recovered Alcohol

Sodium

DEM


19

27.78

92.31

39.37

19.13

8.66

67.17

44.12

35.29

6.47

85.88

37.50

30.00

5.50

73.00

50.00

40.00

11.00

101.00

148.00

140.00

80.00

40.00

408.00

8.00

72.00

36.00

48.00

48.00

212.00

62.40

12.00

112.00

54.80

60.00

100.00

401.20

74.00

6.00

56.00

48.00

80.00

100.00

364.00

10.00

190.00

24.00

80.00



20

Ethylchloride 96.00

Fresh Toluene 6.00

Recovered Toluene 74.00

TOTAL 480.00

46 3,5 Dinitrobenzoic

Acid


Benzoic Acid 24.00

Nitric Acid 135.00

Caustic lye solution 21.00

Total 225.00

47 P Hydroxy

Acetophenone

Anisol 100.00

Aluminium Chloride 0.56

Acetyl Chloride 80.00

Dichloro Methane + Methyl

Chloride 4.00

Recovered Dichloro Methane +

Methyl Chloride 50.00

TOTAL 234.56

48 Cetylpyridinium

Chloride

Cetyl Chloride 30.68

Fresh Pyridine 1.80

Recovered pyridine 16.76

Fresh Methyl ethyl ketone 12.00

Recovered methyl ethyl ketone 148.00

Fresh Acetone 8.00

Recovered Acetone 72.00

TOTAL 289.24

49 Lauryl Pyridinium

Chloride

Lauryl Chloride 28.88

Fresh Pyridine 2.40

Recovered Pyridine 20.00

Fresh Methyl Ethyl Ketone 16.00

Recovered Methyl Ethyl Ketone 144.00

Fresh Acetone 8.00


TOTAL 291.28

50 Ambroxol

Hydrochloride

Ambraxol Base 36.48

Recovered IPA 380.00

Carbon 0.60

HCl 12.00

IPA washing 20.00

TOTAL 449.08

51 ACEBROPHYLLI

NE

Acefilline 16.00

Ambroxol Base 18.40

Carbon 0.60

DMF washing 20.00

Recovered DMF 380.00

TOTAL 435.00

52 3,5 Dibenzyloxy

Acetophenone

Anisol 28.80

3,5 Dribromo Acetophenone 36.00



21

Fresh Toluene 2.00


Sulphuric Acid 0.04

TOTAL 82.84

53 Methyl Nicotinate Nicotonic acid 56.00

Methanol 102.84

Sulphuric acid 42.00

Liquor Ammonia 28.00

Fresh Benzene 4.80

Recovered Benzene 45.20

Total 278.84

54 Furoic Acid Caustic soda 160.00

Chlorine gas 100.00

Furfuraldehyde 120.00

HCl 92.00

Total 472.00

55 1 (2,3 Di chloro

Phenyl) Piperazine

Bydroghloride

2,3 Dichloro Aniline 78.80

Recovered 2,3 Dichloro Aniline 24.00

Fresh orthoxylene 4.00

Bis Salt 75.20

Caustic soda lye 30.00

Caustic soda lye 30.00

Fresh toluene 4.00

Recovered toluene 36.00

Fresh Acetone 4.00


HCl 68.80

TOTAL 410.80

56 1 H 1,2, 4 Triazole Formamide 75.00

Fresh Toluene 3.00


Hydrazine Hydrate 37.50

Fresh IPA 6.00

Recovered IPA 54.00

Total 202.50

57 LASAMIDE Dichloro Benzoic acid 62.40

Chloro Sulphonic acid 320.00

Carbon 0.60

Liquor Ammonia 160.00

HCl 220.00

Total 763.00

58 1 (2,4 Di Chloro

Phenyl) -2 (1

Imidozolyl) Ethanol

Meta Di Chloro benzene 40.00

Aluminium Chloride 48.00

Fresh Hexane 17.20

Recovered Hexane 154.80

Chloro Acetyl Chloride 40.00

Caystic Lye 28.00



22

Soda Ash 44.00

Imidazole 28.00

Fresh Toluene 10.00


Sodium borohydrate 12.00

TOTAL 562.00

59 Fingolimod HCL Methylene chloride 611.12

Octylbenzene 22.35

Aluminium chloride 17.21

Bromoacetyl bromide 25.92

NaHCO3+water 262.62

Sodium sulphate 29.37

Methylene chloride (wash) 183.54

Acetone 246.96

Diethylacetamido malonate 43.86

Potassium carbonate 28.10

Acetone (wash) 100.06

Hexane 1794.38

Hexane (wash) 1158.14

Molecular sieve pellet 9.58

MDC 63.91

Triethylsilane 46.70

MDC 126.26

TiCCl4 47.82

Ethyl acetate 525.84

Ethyl acetate (wash) 1428.52

Silica gel 112.83

TOTAL 6885.10

60 2-

MERCAPTOBENZ

IMIDAZOLE

ODPA 30.40

Carbon Disulfide 28.00

Sodium sulphide 2.24

Sodium Hydroxide(47%) 77.60

TOTAL 138.24

61 Bronopol (BP)

Nitro Methane 66.67

Methanol 13.33

Caustic 66.67

Formaldehyde 9.33

Carbon 29.33

Bromine 0.67

TOTAL 35.33

62 2 Mercapto 5

Methoxy

Benzimimidazone

4-Methyl 2-Nitro Anisidine 40.00

Sodium hydro Sulfide 146.40

Carbon disulfide 30.40

Caustic 3.20

Carbon 1.60

Sulfuric acid 0.80

TOTAL 222.40



23

63 Methyl Acetate

200

Methanol 86.00

Acitic acid 162.00

TOTAL 248.00

64 Ethyl Acetate

Methanol 104.60

Acitic acid 136.40

TOTAL 241.00



24

ANNEXURE VI

BREIF MANUFACTURING PROCESS :

Existing Product:

SODIUM BROMIDE

BRIF PROCESS

First take diluted hydrobromic acid in reactor. Then slowly add sodium hydroxide

solution. When additions completed, and then transfer material in other vessels for

vaporization of water from product. When formation of crystal is started then transfer

mass in crystallizer. Most of material comes in crystal from then centrifuge, drying

and pack material in bags. ML come out from centrifuge will be reused in evaporation

in next batch. Evaporate water will be use in Boiler or Cooling or Solution preparation

or garden.

REACTION

NaOH + HBr NaBr + H2O

40 81 103 18

Flow Diagram:

POTASSIUM BROMIDE

BRIF PROCESS

First take diluted hydrobromic acid in reactor. Then slowly add Potassium hydroxide

solution. When additions completed, and then transfer material in other vessels for

vaporization of water from product. When formation of crystal is started then transfer

mass in crystallizer. Most of material comes in crystal from then centrifuge, drying

Reaction Vessel

Evaporation & Crystallizers

Drying & Packing

NaOH/CaO

Bromin

NaBr



25

and pack material in bags ML come out from centrifuge will be reused in evaporator

in next batch. Evaporate water will be use in Boiler or Cooling or Solution preparation

or garden.

REACTION

KOH + HBr KBr + H2O

56 81 119 18

Flow Diagram:

POTASSIUM SULPHATE

BRIF PROCESS

First take diluted Sulphuric Acid in reactor. Then slowly add potassium hydroxide

solution. When addition completed transfer material in other vessels for vaporization

of water from product. When formation of crystal is started then transfer mass in

crystallizer. Most of material comes in crystal form then centrifuge, drying and pack

material in bags. ML come out from centrifuge will be reused in evaporator in next

batch. Evaporate water will be use in Boiler or Cooling or Solution preparation or

garden.

REACTION

2KOH + H2SO4 K2SO4 + 2H2O

112 98 174 36

Flow Diagram:

Reaction Vessel

Evaporation & Crystallizers

Drying & Packing

NaOH/CaO

Bromin

KBr



26

MAGNESIUM SULPHATE

BRIF PROCESS

First take diluted Sulphuric Acid in reactor. Then slowly add Magnesium Oxide.

When addition completed transfer material in other vessels for vaporization of water

from product. When formation of crystal is started then transfer mass in crystallizer.

Most of material comes in crystal form then centrifuge, drying and pack material in

bags. ML come out from centrifuge will be reused in evaporator in next batch.

Evaporate water will be use in Boiler or Cooling or Solution preparation or garden.

REACTION

MgO + H2SO4 MgSO4 + H2O

40 98 120 18

Flow Diagram:



27

POTASSIUM FLUORIDE

BRIF PROCESS

First take diluted Hydrofluoric Acid in reactor. Then slowly add potassium hydroxide

solution. When addition completed transfer material in other vessels for vaporization

of water from product. When formation of crystal is started then transfer mass in

crystallizer. Most of material comes in crystal form then centrifuge, drying and pack



garden.

REACTION

KOH + HF KF + H2O

56 20 58 18



28

Flow Diagram:

MAGNESIUM SULPHATE

BRIF PROCESS

Diluted Sulphuric Acid is taken in MSRL Vessel. Then manganese oxide powder

(MnO) is added to the mixture with stirring. The reaction takes place and MnO

dissolves in the solution. Remove inorganic impurities by filtration. Solid will be sent

to TSDF site. Transfer material in other vessels for vaporization of water from

product. When formation of crystal is started then transfer mass in crystallizer. Most

of material comes in crystal form then centrifuge, drying and pack material in bags.

ML come out from centrifuge will be reused in evaporator in next batch. Evaporate

water will be use in Boiler or Cooling or Solution preparation or garden.

REACTION

MnO + H2SO4 MnSO4 + H2O

71 98 151 18



29

Flow diagram

CALCIUM SULPHATE

BRIF PROCESS

Lime stone treated with sulphuric acid in an acid resistant MS tank. It takes about 8-

10 Hrs. for reaction to complete. Transfer material in other vessels for vaporization of

water from product. Then transfer reaction mass in centrifuge, drying and pack



garden.

REACTION

CaCo3 + H2SO4 CaSO4 + H2O + CO2

100 98 136 18 44

Flow diagram



30

Proposed Product:

1.Atorvastatin Calcuim

Manufacturing Process :

Stage I:

2-(2-(4-fluorophenyl)-2-oxo-1-phenylethyl)-4-methyl-3-oxo-N-phenylpentanamide

reacts with tert-butyl 2-((4R,6R)-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxan-4-

yl)acetate in presence of pivalic aicd. cyclohexane and Isopropylalcohol gives tert-

butyl2-((4R,6R)-6-(2-(2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)-

1H-pyrrol-1-yl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate.

Stage II:

Tert-butyl 2-((4R,6R)-6-(2-(2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4

(phenylcarbamoyl)-1H-pyrrol-1-yl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate reacts with

water in presence of Acetonitrile, Hydrochloric acid and Sodium carbonate gives

(3R,5R)-tert butyl 7-(2-(4- fluorophenyl)-5-isopropyl-3-phenyl-4-(phenyl carbamoyl)-

1H- pyrrol-1-yl)-3,5- dihydroxy heptanoate.

Stage III:



31

(3R,5R)-tert butyl 7-(2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)-

1Hpyrrol-1-yl)-3,5-dihydroxyheptanoate reacts with water and calcium acetate in

presence of Acetonitrile, Ethyl acetate and sodium hydroxide gives mono calcium

mono (3R,5R)-7-(2-(4-Fluorophenyl)-5-isopropyl-3-phenyl-4--(phenylcarbamoyl)-

1H-pyrrol-1-yl)-3,5-dihydroxy heptanoate). The process flow diagram for

Atorvastatin Calcuim is presented and flow diagram is presented below.

Chemical Reaction:



32



33

Flow diagram:



34

Brinzolomide


Stage I:

4(S)-4-hydroxy-6-sulfonamide dioxide react with Methane sulfonic anhydride and

ethyl

amine in the presence of aq. ammonia and IPA media at 50 degrees and compound

isolating

with adjusting the mass PH with HCl in the presence o f IPA to give Brinzolamide.

Schematic diagram of Brinzolamide and flow diagram for Brinzolamide is given

below.

Chemical Reaction:



35

Flow diagram

Canagliflozin


2-(5-bromo-2-methyl benzyl)-5-(4-flurophenyl) thiophene react with silyl-D-

gloconolactone in the presence of Methanol media and potassium carbonate catalyst

and compound isolate in Acetone media to give pure Canagliflozin. Schematic

diagram of Canagliflozin and flow diagram for Canagliflozin is presented below.



36

Chemical Reaction:

Flow diagram

Capacitabine


2,3-di-o-acetyl-5-deoxy-5-fluorocytidine is condensed with n-Pentylchloroformate in



37

Methylene chloride to give Capecitabine (Pharma). Schematic diagram of

Capecitabine and flow diagram for Capecitabine is presented below.



38

Flow diagram

Cefsulodine Sodium


Stage I:

RS-a- Sulfophenyl acetic acid react with S- Methyl benzyl amine in the presence of

acetonitrile media at room temperature to give complex com stage-I.

Stage II:

1-Hydroxy benzotraizole react with methan sulphonyl chloride in the presence of

sodium

bicarbonate base and MDC media at 50 degrees then mass adjusting the PH with

sodium bi

carbonate and at room temperature and compound isolate in Hexane media to give

stage-II

solid.

Stage III:

7-Amino cephalosporonic acid react with tert-butyl acetate in the presence of boron

trifluoro etharate catalyst and Hexane media at 65 degrees to give stage-III solid.

Stage IV:



39

Stage-I react with stage-II and stage-III in the presence of zinc chloride catalyst and

triethyl

amine base in MDC media and compound isolate in Ethyl acetate and hexane and di

isopropyl ether media to give stage-IV solid.

Stage V:

Stage –IV react with dimethyl amine formamine in the presence of pyridine-4-

carboxamide

and sodium iodide catalyst in Ethanol media then compound isolating with using

concentrated hydrochloric acid.

Stage VI:

Stage-V reacts with sodium acetate at 40 degrees and compound isolating ethanol

media to

give Cefsulodin pure compound. The process flow diagram for

and flow diagram is presented below.



40

Chemical Reaction:



41



42

Flow diagram:



43

Dabigatran


Stage-I:

The propanoic acid methyl ester derivate of formulae-I is dissolved in ethanol and

acetic

acid, hydrogenated with damp Pd/C at RT at 2 bar hydrogen pressure. After

completion of

the reaction the catalyst is filtered off and dissolved in ethanol was added to filtrate.

To get

formulae-II precipitated out which was filtered off and dried.

Stage-II:

The Tosylate salt obtained in the stage I was dissolved in acetone and the mixture is

combined with hexyl chloroformate in presence of potassium hydroxide at

temperature

15oC. After completion of the reaction the precipitated product is filtered off and

washed

with acetone mixture. The resulting crude is crystallized with water. Schematic

diagram of

Dabigatran and flow diagram for Dabigatran is presented below.

Chemical Reaction:



44

Flow diagram:

Dapoxetine Hydrochloride


�-(dimethylamino) benzenepropanol is reacted with 1-fluoronaphthalene in presence

of sodium hydroxide, followed by treated with hydrochloric acid in dimethyl

sulfoxide to yield Dapoxetine Hydrochloride (Pharma). Schematic diagram of

Dapoxetine and flow diagram for Dapoxetine Hydrochloride is presented below.

Chemical Reaction:



45

Flow diagram:



46

Darunavir


Stage-I:

(3aS,4S,6aR)-4-methoxy-terahydrofuro-[3,4-b]furan-2-(3H)one is reacted with

NaBH4 and Hydrochloric acid in presence of tetrahydrofuran to give (3R,3aS,6aR)-

hexahydrofuro[2,3-b]furan-3-ol.

Stage-II:

4-Amino-N-(2R,3S)(3-amino-2-hydroxy-4-phenyl-butyl)-N-isobutyl-

benzenesulfonamide is condensed with (3R,3aS,4aR)-hexahydrofuro[2,3-b]furan-3-ol

in the presence of disucinimidyl carbonate to yield Darunavir (Pharma). Schematic

diagram of Darunavir and flow diagram for Darunavir is presented below.

Chemical Reaction:



47

Flow diagram:



48

Dexlansoprazole


2-[3-Methyl-4-(2,2,2-trifluoro-ethoxy)-pyridin-2-ylmethanesulfinyl]-1H-

benzoimidazole is treated with (+)Diethyl tartarate, titanium isopropoxide, triethyl

amine and L(+) mandelic acid in presence of acetone to get Dexlansoprazole

mandelate salt, which is on neutralization with sodium bicarbonate in DCM yielded

Dexlansoprazole. Schematic diagram of Dexlansoprazole and flow diagram for is

presented below.

Chemical Reaction:



49

Flow diagram

Diacerein


Aloe emodine is oxidized using chromic acid and tetrahydrofuran as a solvent to give

DCN-I (4,5-bis (Hydroxy)-9,10-dihydro-9, 10-dioxo-2-anthracenecarboxylic acid).

DCN-I is reacted with propionic anhydride in presence of sulfuric acid to get DCN-II

(9, 10- dioxo-4,5-dipropanoyloxyanthracene-2-carboxylic acid).

DCN-II is purified in THF and then hydrolyzed using sodium hydroxide in water to

give DCN-IV (4,5-dihydroxy-9,10-dioxoanthracene-2-carboxylic acid).

DCN-IV is reacted with acetic anhydride in presence of sulfuric acid to get Diacereine

crude and which is first purified with NMP & methanol mixture and then with NMP

& water mixture. Schematic diagram of Diacerein and flow diagram for Diacerein is

presented below.



50



51



52

Flow diagram



53

Dorzolamide HCl


Stage-I: (±)-Trans-5,6-dihydro-4H-4-Ethyl amino-6-methylthieno[2,3-b] thiopyran-2-

sulfonamide-7,7-dioxide is resoluted with (-)-Di-para-toluoyl-L-tartaric acid

monohydrate

and then reacted with hydrochloric acid in presence of water to yield Dorzolamide

Hydrochloride (Pharma). Schematic diagram of Dorzolamide Hydrochloride and flow

diagram for Dorzolamide Hydrochloride is presented below.

Flow diagram



54

Dapagliflozin


Stage-I:

Intermediate-I react with Intermediate-II in the presence of n-butyl lithium, triethyl tin

hydride and trifluro borate catalyst and Toluene media at 60 degrees and compound

isolate

in acetonitrile and MDC media to give Dapagliflozin. Schematic diagram of

Dapagliflozin

and flow diagram for Dapagliflozin is presented below.

Chemical Reaction:



55

Flow diagram

Esomeprazole Magnesium Dihydrate

Stage-I:

5-Methoxy-2-[[(4-methoxy-3,5-diemthylpyridin-2-yl)methyl]thio]-1H-benzimidazole

is

oxidized with hydrogen peroxide in presence of vanadium acetyl acetonate in acetone

and

methanol to yield (+)-Omeprazole (Stage-I compound).

Stage-II:

(±) Omeprazole is resoluted with (S)-(-)-1,1-Bi-2-Naphthol in methylene chloride and

toluene and then treated with magnesium chloride and water to yield Esomeprazole

Magnesium (Pharma). Schematic diagram of Esomeprazole Magnesium and flow

diagram for Esomeprazole Magnesium is presented below.



56

Chemical Reaction:



57

Flow diagram:

Irbesartan


Stage-I:

2-butyl-1,3-diazaspiro[4,4]non-1-ene-4-one hydrochloride is condensed with 5-[4'-

(bromomethyl)biphenyl-2-yl]-1-trityl-1H-tetrazole in the presence of methanolic



58

hydrochloric acid to give Irbesartan. Schematic diagram of Irbesartan and flow

diagram for Irbesartan is presented below.



59

Flow diagram:

Montelukast Sodium


Stage-I:

2-[2-3(S)-[3-[2-(7-chloro-2-quinolinyl)-ethyl]phenyl]-3-hydroxy propyl]phenyl-2-

propanol is

condensed with 2-[1-(sulfonyl methyl) cyclopropyl]acetic acid in presence of

Toluene,

Acetonitrile and reacted with Sodium hydroxide in presence of methanol to give

Montelukast Sodium (Pharma). Schematic diagram of Montelukast Sodium and flow

diagram for Montelukast Sodium is presented below.



60

Chemical Reaction:

Flow diagrm:



61

Posaconazole


N-{4-[4-(4-Hydroxy-phenyl)-piperazin-1-yl]-phenyl}-carbonic acid phenyl ester is

condensed with Formic acid N'-(2-benzyloxy-1-ethyl-propyl)-hydrazine and (5R-cis)-

5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)tetrahydrofuran-3-methanol

tosylate ester in the presence of Tetrahydrofuran and Formic acid to yield

Posaconazole (Pharma). Schematic diagram of Posaconazole and flow diagram for

Posaconazole is presented below.



62

Chemical Reaction:



63

Flow diagram

Quetiapine Hemifumarate


Stage-I:

Dibenzo-(1,4)-thiazepine-11(10H)-one is condensed with 2-(2-(piperazin-1-

yl)ethoxy)ethanol is treated with fumaric acid in presence of thionyl chloride and

ethanol to give Quetiapine Hemifumarate. Schematic diagram of Quetiapine

Hemifumarate and flow diagram for Quetiapine Hemifumarate is presented below.



64

Chemical Reaction:

Flow diagram:



65

Risedronate Sodium


Stage-I:

A mixture of 3- pyridylacetic acid, H3PO3, diethyl carbonate we stirred for 5-10

minutes at room temperature. PCl3 was added drop wise between 25-35°C To the

resulting reaction mixture; methanesulfonic acid was added drop wise between 40-

55°C. Reaction mixture was heated to 60-65°C for 1.0-1.5h. Further the reaction mass

was heated to 70-75°C for 4.0- 6.0h. After reaction completion, pre chilled water (70

ml) was added at 65-80°C in a drop wise manner and diethyl carbonate layer was

separated. To the resulting aqueous layer hydrochloric acid (10ml) was added and

heated to reflux for 10-15hrs and cooled to 0-15°C. Residronic acid was ejected; from

the resulting aqueous reaction mass at a pH of 1.4-1.8. The resulting suspension was

filtered and slurried in water then dried to obtain Risedronic acid.

Stage-II:

Output from stage 1 is taken in DI Water and reacted with aqueous Sodium

Hydroxide solution. The material is isolated in presence of Water, Iso propyl alcohol

mixture to get form A of hemipenta-hydrate at 14-18°C and filtered at 0-5°C. Wet

material is taken for reslurry water, Isopropyl alcohol at 14-18°C and filtered through

PNF. Wet material is dried in FBD at 40-45°C with air 55±5 % RH to reach to LOD

of 10-15 %. Schematic diagram of Risedronate Sodium and flow diagram for

Risedronate Sodium is presented below.

Reaction



66

Flow diagram:



67



68

Telmisartan


Stage-I:

1H-Benzimidazole-2n-propyl-4-methyl-6-(1-methyl benzimidazole-2yl] is Condensed

with

4-methyl-(bromomethyl) bi phenyl carboxylate in the presence of Methyl Isobutyl

Ketone

to form a 1-[4-(1,4-Dimethyl-2-propyl-1H-[2,5]bibenzoimidazolyl-1-yl methyl)-

biphenyl-2-

yl]ethanone [Telmesartan Ester]

Stage-II:

1-[4-(1,4-Dimethyl-2-propyl-1H-[2,5]bibenzoimidazolyl-1-ylmethyl)-biphenyl-2-

yl]ethanone

[Telmesartan Ester ] Hydrolysis with Potassium Hydroxide to form a 2-(4-{[4-methyl-

6-(1-

methyl-1H-1,3-benzodiazol-2-yl)-2-propyl-1H-1,3-benzodiazol-1-

yl]methyl}phenyl)benzoic

acid [ Telmisartan ]

Stage-III:

2-(4-{[4-methyl-6-(1-methyl-1H-1,3-benzodiazol-2-yl)-2-propyl-1H-1,3-benzodiazol-

1-yl]

methyl} phenyl) benzoic acid [ Telmisartan ] purification in methanol to form a 2-(4-

{[4-

methyl-6-(1-methyl-1H-1,3-benzodiazol-2-yl)-2-propyl-1H-1,3-benzodiazol-1-

yl]methyl}

phenyl) benzoic acid [ Telmisartan ]. Schematic diagram of Telmisartan and flow

diagram for Telmisartan is presented below.



69

Chemical Reaction:



70

Flow diagram



71

Vilazodone hydrochloride


Stage-I:

5-{4-[4-(5-Cyano-1H-indol-3-yl)-butyl]-piperazin-1-yl}-benzofuran-2-carboxylicacid

methyl ester reacts with methanolic ammonia to yield 5-{4-[4-(5-Cyano-1H-indol-3-

yl)-butyl]- piperazin-1-yl}-benzofuran-2-carboxylic acid amide.

Stage-II:

5-{4-[4-(5-Cyano-1H-indol-3-yl)-butyl]-piperazin-1-yl}-benzofuran-2-

carboxylicacidamide reacts with IPA/HCl in methanol and water to yield Vilazidone

hydrochloride. Schematic diagram of Vilazidone hydrochloride and flow diagram for

Vilazidone hydrochloride is presented below.



72

Flow diagram:

BOSENTAN

Manufacturing Process

Guiacol and diethyl chloromalonate were added drop wise in succession to a

previously prepared sodium ethoxide solution. The suspension was stirred at 45oC

with exclusion of moisture. Thereafter the ethanol was distilled off. The residue was

taken up in toluene, wash with water and 1% sodium hydroxide solution until organic

phase gets colorless. Finally wash with water and sat. brine solution. After drying on

sodium sulfate and evaporating the solvent, the residue was distilled to give diethyl

(O‐ethoxyphenoxy) malonate. Pyrimidine‐2‐carboxamidine hydrochloride and diethyl

(O‐ethoxyphenoxy)malonate were added while cooling with ice to a previously

prepared sodium methoxide solution from sodium and absolute methanol. Stir the

reaction mixture at room temperature with the exclusion of moisture. Solvent was

evaporated under reduced pressure. The residue was taken up in 1N NaOH solution.

Alkaline solution was acidified with 1N HCl. Precipitate was filtered off and

washed thoroughly with water and dried under vacuum. The

5‐(2‐methoxy‐phenoxy)‐2‐ (pyrimidin‐2‐yl) tetrahydro‐pyrimidine‐4,6‐dione used in

the next step without further purification. Pyrimidinone from step‐II was charged in to



73

N, N diisopropyl‐N‐ethylamine. Phosphorous pentachloride (PCl5) was added portion

wise. Reflux the reaction mixture. The mixture was then evaporated under reduced

pressure. Residue was poured on to ice and extracted with ethyl acetate.

The combined extracts were washed with water, dried and evaporated in a vacuum.

The residue was chromatographed on silica gel using ethyl acetate yielded

4,6‐dichloro‐5‐(2‐methoxy‐phenoxy)‐2,2’‐bipyrimidine. To a solution of Step‐III in

DMSO, p‐tert‐butylbenzenesulphonamide was added. The mixture was heated at

100oC. The solution was concentrated under vacuum. The oily residue was poured on

to ice, and adjusted

pH 3. The suspension was extracted with ethyl acetate, combined organic layers and

washed with water. Dried over sodium sulphate and concentrated under reduced

pressure. The residue was chromatographed on silica gel with toluene‐ethyl acetate

9:1to give

4‐tert‐butyl‐N‐[6‐chloro‐5‐(2‐methoxy‐phenoxy)‐2‐(pyrimidin‐2‐yl)‐pyrimidin‐4‐yl]‐

benzenesulphonamide.

To a solution of sodium metal in ethylene glycol, charged Step 04. The mixture was

heated at 100oC. After completion of reaction, the reaction mass was poured on to ice

and adjusted to PH=3 with 1M tartaric acid. The suspension was extracted with ethyl

acetate. Combined organic layers were washed with water, dried over sodium sulphate

and concentrated under reduced pressure. The residue was chromatographed on silica

gel with dichloromethane‐‐ethyl acetate 9:1 to yield

4‐tert‐butyl‐N‐[6‐(2‐hydroxy‐ethoxy)‐5‐(2‐methoxy‐phenoxy)‐2‐(pyrimidin‐2‐yl)‐

pyrimidin‐4‐yl]‐benzenesulphonamide (Bosentan)



74

Chemical Reaction



75



76

Flow diagram



77

FESOTERODINE NDMF


Stage‐‐‐‐I: Preparation of FES/KSM/I (Ester):

Reaction of Cinnamic acid with p‐Cresol in presence of Sulphuric acid gives

Coumarin

intermediate which on further reaction with Benzyl bromide in presence of Methanol

and base

gives Ester is isolated from Methanol.

Stage‐‐‐‐II: Preparation FES/KSM/II (Amide):

Ester is hydrolyzed using Potassium hydroxide and Methanol to give Acid

intermediate which on

further reaction with Thionyl chloride followed by reaction with Diisopropylamine

gives amide.

Amide is isolated from Isopropanol.

Stage‐‐‐‐III: Preparation of FES/KSM/III (KSM):

Amide on reduction with Sodium Borohydride and Borontrifluoride etherate gives

Amine (Oil)

having one chiral carbon and it is racemic. Racemic Amine (Oil) on resolution with

optically

active acid Di p‐toluoyl L‐tartaric acid followed by crystallizations gives KSM of

desired optical

and chemical purity.



78

Chemical Reaction



79

Flow diagram

63.FESOTERODINE FUMARATE

Manufacturing Process:

Step-II: Reduction and Debenzylation

Manufacture of R-(+)-2-(3-Diisopropylamino-1-phenylpropyl)-4-hydroxy methyl

phenol (Fesoterodine Fumarate Stage-II)

1 mole (R)-(-)-4-benzyloxy-3-(3-diisopropylamino-1-phenyl-propyl)-benzoic acid

methyl ester reacts with 1 mole Lithium Aluminium Hydride with 2 mole of water

media resulting 1 mole of intermediated (Fesoterodine Fumarate stage-I with the by-

product 1 mole Lithium Hydroxide and 1 mole Aluminium Hydroxide.

9.Further, 1 mole of above intermediate reacts (in-situ) with 1 mole Hydrogen (gas) in

the solvent media finally resulting 1 mole R-(+)-2-(3-Diisopropylamino-1-



80

phenylpropyl)-4-hydroxy methylphenol (Fesoterodine Fumarate Stage-II) with the by-

product 1 mole Toluene.

Step-Final: Etherification and Salt formation

Manufacture of R-(+)-2-(3-Diisopropylamino-1-phenylpropyl)-4-

hydroxymethylphenyl isobutyrate hydrogen fumarate (Fesoterodine Fumarate

Stage-Final)

1 mole Fesoterodine fumarate stage-ii reacts with 1 mole Isobutyryl chloride in the

solvent media gives 1 mole of intermediated stage Fesoterodine free base with the by-

product 1 mole HCl which finally reacts (in-situ) with 1 mole Fumaric acid which

gives desired Fesoterodine Fumarate Stage-Final.

Chemical Reaction: Fesoterodine Fumarate, Stage-2

+

O

O

CH3

O

N

CH3 CH3

CH3

CH3

R-(-)-4-benzyloxy-3-(3-Diiso- propylamino-1-phenyl-propyl)- benzoic acid methyl ester

MF:C30H37NO3

FW:459.62

LiAlH4 +

Lithium Aluminium HydrideMF:LiAlH4

FW:37.95

2H2O

WaterMF:H2O

FW:2X18(36)

R-(+)-4-benzyloxy-3-(3-Diisopropyl- amino-1-phenyl-propyl)-phenyl methanol

MF:C29H37NO2

FW:431.60

OH

O

N

CH3 CH3

CH3

CH3

LiOH

Lithium HydroxideMF:LiOH

FW:23.95

Al(OH)3

Aluminium hydroxide

MF:Al(OH)3

FW:78

+ +

R-(+)-4-benzyloxy-3-(3-Diisopropyl- amino-1-phenyl-propyl)-phenyl methanol

MF:C29H37NO2

FW:431.60

OH

O

N

CH3 CH3

CH3

CH3

H2

FW:2.01

Hydrogen (gas)

MF:H2

CH3

FW:92.14

MF:C8H7

Toluene

+

Fesoterodine Fumarate, Stage-2

OH

OH

N

CH3 CH3

CH3

CH3

MF:C22H31NO2

FW:341.49

+

Fesoterodine Fumarate, Stage-Final

Fesoterodine Fumarate, Stage-2

OH

OH

N

CH3 CH3

CH3

CH3

MF:C22H31NO2

FW:341.49

+

CH3 CH3

O

Cl

Isobutyl chloride

MF:C4H7ClO

FW:106.55

OH

O

N

CH3 CH3

CH3

CH3

CH3

CH3 O

FW:411.58

MF:C26H37NO3

R-(+)-2-(3-Diisopropylamino-1-phenyl-propyl)-4-hydroxymethyl phenol isobutyrate ester

H Cl

Hydrochloric acid

MF:HCl

FW:36.5

+

OH

O

N

CH3 CH3

CH3

CH3

CH3

CH3 O

FW:411.58

MF:C26H37NO3

R-(+)-2-(3-Diisopropylamino-1-phenyl-propyl)-4-hydroxymethyl phenol isobutyrate ester

+

O

OH

O

OH

MF:C4H4O4

FW:116.07

Fumaric Acid

OH

O

N

CH3 CH3

CH3

CH3

CH3

CH3 O

O

OH

O

OH

MF:C30H41NO7

FW:527.65

Fesoterodine Fumarate, Stage-Final

Flow diagram:



81



82



83



84



85



86

Vildagliptin


Stage‐I

Reaction of (2S)‐1‐(chloroacetyl)‐2‐cyanopyrrolidine (KSM‐II) with

3‐Amino‐1‐hydroxy adamantine (KSM‐I) in presence of Potassium Carbonate and

Dimethyl Formamide (DMF) as a solvent gives Vildagliptin crude.

Stage‐II

Vildagliptin crude is purified by treatment of Aq. Potassium Hydrogen Sulphate and

Aq. Potassium Carbonate in presence of Dichloromethane, followed by Acetone

crystallization to give Vildagliptin API.

Chemical Reaction



87



88

RIVASTIGMINE TARTRATE


Stage‐‐‐‐I (Rivastigmine Tartrate Crude)

Carbamoylation of (S)‐3‐(1‐dimethyl amino ethyl) phenol carried out with

N‐ethyl‐N‐methyl Carbamoyl chloride in Toluene using Triethylamine as base and

4‐dimethyl amino pyridine as catalyst at 60‐65°C. After completion of reaction cool

reaction mass to 25‐35°C, filter the reaction mass, wash the solid salt with Toluene.

Charge water in to the filtrate, stir and separate layers. Wash the organic layer with

Sodium bicarbonate solution, Hydrochloric acid solution and then water and than

charcoalized with activated charcoal. Distill out toluene from filtrate to obtain

Rivastigmine Base. Charge Denature spirit and L (+) tartaric acid in Rivastigmine

Base, and heat to 55‐60°C to get clear solution and than charge Ethyl acetate,

Cool to 40°C and seed the reaction mass with Rivastigmine Tartrate, cool to 0‐5°C

and stir for 4‐ 5 hours, filter, Wash with Ethyl acetate and dry the crude Rivastigmine

Tartrate at 40‐50°C in



89

vacuum oven.

Stage‐‐‐‐II (Rivastigmine Tartrate)

Dissolve Rivastigmine Tartrate in Ethyl Alcohol, heat to 55‐60°C to get clear

solution, charcoalized and distill out Ethyl Alcohol. Charge Ethyl Alcohol , heat to

55‐60°C and than charge Ethyl acetate, Cool to 40°C and seed the reaction mass with

Rivastigmine Tartrate, cool to 0‐5°C and stir for 4‐5 hours, filter, Wash with Ethyl

acetate and dry the Rivastigmine Tartrate at 40‐50°C in vacuum oven till constant

weight.

Chemical Reaction



90

FLOWDIAGRAM

FEBUXOSTATE


Ethyl‐2‐(3‐formyl‐4‐isobutoxyphenyl)‐4‐methylthiazole‐5‐carboxylate is reacted with

hydroxylamine hydrochloride to form oxime which is dehydrated with sodium

formate & formic acid to form

Ethyl2‐(3‐cyano‐4‐isobutoxyphenyl)‐4‐methyl‐5‐thiazolecarboxylate which on

hydrolysis gives Febuxostate.

Chemical Reaction



91



92



93

FLOW DIAGRAM

AGOMELATINE


Catalytic hydrogenation of (7‐Methoxy‐1‐naphthyl) acetonitrile using Methanol and

Ammonia gives 2‐(7‐Methoxy‐1‐naphthyl) ethanamine. Condensation of

2‐(7‐Methoxy‐1‐naphthyl) ethanamine with acetyl chloride in presence of base gives

crude Agolelatine. Which on purification gives final Agomelatine API.

Chemical Reaction:



94



95

FLOWDIAGRAM

LEVETIRACETAM


Stage‐‐‐‐I

S(+)‐2‐amino butyramide Hydrochloride reacts with 4‐chloro Butyryl chloride in

presence of Tetra butyl ammonium bromide, potassium hydroxide to give the

Levetiracetam crude (Stage‐I).

Stage‐‐‐‐II

Levetiracetam crude is purified by charcoal treatment with Dichloromethane solvent.

Then Dichloromethane is completely distilled out and finally crystallized in Ethyl

Acetate to give the Levetiracetam API.



96

Chemical Reaction



97

Flow diagram



98

BOSENTAN


To sodium glycolate solution added bipyrimidine t-butyl sulfonamide. Stirred the

reaction mass at 95°C for 4 hours. Distilled out ethylene glycol to obtained residue,

which is dissolved in ethyl acetate and washed with 1N HCl. Organic layer is dried

and concentrated under vacuum. To the residue added diisopropyl ether and stirred for

1 hr, Solid precipitate out. Filtered the solid and dried the material under vacuum at

40°C.



99

Chemical Reaction:

Flow diagram

ON

NN

N

OCH3

Cl

NHS

O

O

CH3

CH3CH3

ONa

ONa

ON

NN

N

OCH3

O

NHS

O

O

CH3

CH3CH3

ONaFormula Weight = 526.00716

106.03 + NaCl

Formula Weight = 573.59

58.44

di pyrimidine t-Butyl sulfonamide

ClH

36.5

ON

NN

N

OCH3

O

NHS

O

O

CH3

CH3CH3

OH

+NaCl58.44

BosentanFormula Weight = 551.61

Sodium glycolate



100

Flow diagram



101

METHYL PARABEN


PHBA and Methanol react with each other in a closed reactor at a reflux

temperature.After completion of reaction the resultant mass is cooled to room

temperature and centrifuge. The filtrates is used for the next batch. The solid mass

,MethylParaben is washed with Soda bicarbonate solution to remove acidity from the

material. It is washed with plain water .All washing are transferred to effluent

collection Tank, The solid material is dried and packed as Methyl Paraben.

Chemical Reaction:

C7H6O3 + CH3OH C8H8O3 + H2O

Flow Diagram

ETHYL PARABEN


PHBA and ethanol react with each other in a closed reactor at a reflux temperature.

After completion of reaction the resultant mass is cooled to room temperature and

centrifuge. The filtrate is used for the next batch. The solid mass, Ethyl Paraben is

washed with Soda bicarbonate solution to remove acidity from the material. It is

washed with plain water .All washing are transferred to effluent collection Tank, The

solid material is dried and packed as Ethyl Paraben

PHBA

Methanol

Reactor

Centrifuge

Washing

Dryer

Methyl Paraben

Wash With Water

Wash With NaHCo3solun

Effluent to CEPT

Evaporation loss 50kgs

Methanol



102

Chemical Reaction:

C7H6O3 + C2H5OH C9H10O3 + H2O

Flow Diagram

PROPYL PARABEN


PHBA and Propanol react with each other in a closed reactor at a

refulxtemperature.After completion of reaction the resultant mass is cooled to room

temperature and centrifuge. The filtrate is used for the next batch. The solid mass,

Propyl Paraben is washed with Soda bicarbonate solution to remove acidity from the

material. It is washed with plain water.All washing are transferred to effluent

collection Tank, The solid material is dried and packed as Propyl Paraben.

Chemical Reaction:

C7H6O3 +C3H8O C10H12O3 + H2O

Flow Diagram

PHBA

Ethanol

Reactor

Centrifuge

Washing

Dryer

Ethyl Paraben

Wash With Water

Wash With NaHCo3soln

Effluent to CEPT

Evaporation loss

Ethanolmls



103

PHBA

N-Propanol

Reactor

Centrifuge

Washing

Dryer

Propyl Paraben

Wash With Water

Wash With NaHCo3solun

Effluent to CEPT

Evaporation loss

N-Propanol Mls



104

BUTYL PARABEN

Manufacturing Process:

PHBA andbutanol react with each other in a closed reactor at a reflux temperature.

After completion of reaction the resultant mass is cooled to room temperature and

centrifuge. The filtrates is used for the next batch. The solid mass ,ButylParaben is

washed with Soda bicarbonate solution to remove acidity from the material. It is

washed with plain water .All washing are transferred to effluent collection Tank, The

solid material is dried and packed as Butyl Paraben

Chemical Formula

C7H6O3+ CH3(CH2)3OH C11H14O3 + H2O

FlowDiagram

ISO PROYL PARABEN


PHBA and Isopropanol react with each other in a closed reactor at a reflux

temperature. After completion of reaction the resultant mass is cooled to room

temperature and centrifuge. The filtrate is used for the next batch. The solid mass,

Methyl Paraben is washed with Soda bicarbonate solution to remove acidity from the

PHBA

Butanol

Reaction

Centrifuge

Washing

Dryer

s

Butyl Paraben

Wash With Water

Wash With NaHCo3sol

Effluent to CEPT

Evaporation loss

105kgs

Mls of

butanol



105

material. It is washed with plain water .All washing are transferred to effluent

collection Tank, The solid material is dried and packed as Methyl Paraben

Chemical Reaction:

C7H6O3 + CH3CH3 CHOH C10H12O3 + H2O

Flow Diagram

PHBA

Iso

propanol

Reaction

Centrifuge

Washing

Dryer

IsoPropyl Paraben

Wash With Water

Wash With NaHCO3Sol.

Effluent to CEPT

Evaporation loss

Iso propanelmls



106

Chlorohexidine Base (CH-Base)


1. Charge N-Butanol, Hexa Methyl Diamine, Tri Ethyl Amine, Sodium Di Cynamide in

the Reactor.

2. Start addition of HCL.

3. Slowly start heating upto distillation of butanol at 1200C.

4. Reflux the reaction mass for 4 Hrs at 1180C to 124

0c.

5. Cool the reaction mass below 800C.

6. Add PCA HCL & Caustic solution.

7. Wash the reaction mass with water.

8. Separate the aqueous layer.

9. Cool the reaction mass upto 480C.

10. Centrifuge the material. Wash the cake with methanol.

11. Centrifuge, drying and pack the material.

12. Final Yield: 500 kg.

Chemical Reaction:

CH 3 NO2 + 2 H C HO HOCH2CH CH 2OHN O2 NaO H (M W. 40)Br2(M W.1 6 0)N O2 HOCH 2 C - C H 2 OH + Na Br + H2O(M W. 6 1) (M W. 60) (M W. 1 21)

Br(MW. 20 0 ) ( M W. 1 0 3 )



107

Flow Diagram:

Stage 1

HEXA METHYL DI AMINE

SODIUM DI CYNAMIDE

N BUTANOL

TRI ETHYL AMINE

SODIUM HYDROXIDE

FLAKES

WATER

PCA HCL

GLR-1

REACTOR

GLR-1

REACTOR

SSR

REACTOR



108

Stage 2

FILTERATE

NaOH

Salt

Butanol

Water

SDC

HMDA

TEA

WASHING

Salt

Butanol

Water

SDC

SSR

BASKET

CENTRIFU

SE CAKE

Crude CH Base

Butanol

Water

HMDA

Salt

SSR

REACTOR

CAKE Crude CH Base

Butanol

Water

IMP

Methenol

SSR

BASKET

CENTRIFU

SE

CAKE Crude CH Base

Butanol

Water

Methenol

FILTERATE Crude CH Base

Butanol

Water

IMP

Methenol



109

LEVOSULPIRIDE


Charge Mono ethylene glycol in the reactor ,start stirring and charge slowly 2-

methoxy-5 sulphomyl methyl benzoate powder .Add slowly and gradually liquid ( S-)

1 –ethyl-2-aminomethylpyrolindine within 15 -20 min. Start heating and maintain at

60-70 °C for 8 hrs. Cool it up to 35 °C centrifuge it ,mother liquor is reused for next

batch. dry , pulverized and packed as Levosulpiride.

Chemical Reaction:

C9H11O5NS + C7H17N2 ↑C15H23N3O4S + CH3OH

SSR

FDP

CAKE Crude CH Base

Butanol

Water

Methenol

CAKE

Crude CH Base

Butanol

Water

Methenol

CAKE Crude CH Base

Water

Methenol



110

Flow diagram

PANTAPRAZOLE SODIUM


STAGE-1

2-Chloromethyl-3,4-dimethoxy pyridine hydrochloride is reacted with 5-

difluoromethoxy- 2-mercapto benzimidazole in aqueous methanol in presence of

sodium hydroxide r to get the desired product.

STAGE-2

Pantoprazole sulfide is treated with Sodium hypoclorite solution in DCM-water

mixture at 0 to -5o C in presence of Aqueous sodium hydroxide and after completion

of reaction, the reaction mixture is quenched by the addition of aqueous sodium

thiosulfate solution. To the resulting reaction mixture is added DCM and water and

the reaction stirred for 30 minutes. The layers are separated. To the aqueous layer is

added fresh DCM and the pH of the resulting reaction mixture is adjusted to 9 to 9.5

by the addition of acetic acid and stirred for 30 minutes. Layers are separated and the

aqueous layer is again extracted with fresh DCM. The DCM extracts obtained after

the pH adjustment are combined and concentrated up to about 3 times volume of the

substrate. To the concentrated reaction mixture is added IPE to precipitate the

Mono ethylene Glycol

Methoxy Ester

Reactor

Dryer

Pulvrised

Amino

Pyrrolidine

Levosulpiride

Centrifuge MLS re

used in

next batch

Evoparation loss



111

product, which is filtered, and the obtained solid washed with IPE and dried to get

Pantaprazole base.

STAGE-3

Pantaprazole sodium is prepatred by dissolving pantaprazole base in ethyl acetate and

adding sodium hydroxide solution, some ethyl acetate is distilled out to get solid

pantaprazole sodium. After filtration and washing with E a, pure pantaprazole Sodium

is obtained.

STAGE-4




is obtained.

STAGE-5




is obtained.

Chemical Reaction:

N

OCH3OCH3

Cl

.HCl

+

N

NH

SH

OCF2H

Methanol / Water

Aq. NaOHN

OCH3OCH3

N

NH

S

OCF2H

Pantoprazole sulfide

N

OCH3OCH3

N

NH

S

OCF2H

N

OCH3OCH3

S

O N

NH

OCF2H

N

OCH3OCH3

S

O N

NH

OCF2H

N

OCH3OCH3

S

O N

N

OCF2H

- 1. 5 H2O


Sodium hypochlorite (74.5)

DCM / Water / 2 NaOH(80)

Triethyl benz. ammon. chloride

IPE

Ethyl acetate

Aq. NaOH

Pantoprazole sodium

Pantoprazole base

Pantoprazole base

Pantoprazole sodium

2-(chloromethyl)-3,4-dimethoxypyridine

5-(difluoromethoxy)-1H-benzimidazole-2-thiol

m.wt= 224.08m.wt= 216.20

m.wt = 367.37

Pantoprazole sodium


m.wt = 367.37 m.wt = 383.36

Pantoprazole base

m.wt = 383.36 m.wt = 409.36

+ 2HCl

72.91

+2NaCl + NaOH + Na 2S4O6 + CH3COONa + 2H 2O58.5 40 270 82 36



112

Flow Diagram



113



114

CILNIDIPINE


Charge Toluene in the reactor ,start stirring and charge slowly 3-Nitro .Add slowly

and gradually 3-Amino within 1-2 hrs.Start heating and maintain at 80-90°C for 10

hrs. Cool it up to 35°C, centrifuge it ,mother liquor is reused for next batch, dry ,

pulverized and packed as Cilnidipine.

Chemical Reaction:

C14H16NO6 + C13H15NO2 C27H28N2O7 + H2O

Flow Diagram

Methyl Acetate


Methanol reacts with Acetic acid to get Methyl Acetate and release water.

Chemical Reaction

Toluene

3-Nitro

Reactor

Dryer

Pulvrised

3-Amino

Cilnidipine

Centrifuge MLS

reused in

next batch

Evoparation loss



115

Flow Diagram

Ethyl Acetate


Ethanol reacts with Acetic acid to get Ethyl Acetate and release water.

Chemical Reaction

Flow Diagram

FINGOLIMOD HYDROCHLORIDE


Stage: 1

Charge MDC, Octylbenzene, anhydrous Aluminium chloride &Bromoacetyl Bromide

in to reactor, stir & heat the content. After completion of reaction, charge purified

water in to reactor, stir the content and separate the Aq. Layer & organic layer. Distil

out solvent completely and unload the material as FingolimodHCl stage-1.

Stage: 2

Ethyl Acetate

CH3CH2OH + CH3COOH CH3COOCH2CH3 + H2O

Ethanol Acetic Acid Ethyl Acetate Water

M.W. 46 M.W. 60 M.W.88 M.W.18

M e th y l A c e ta te

C H 3 O H + C H 3 C O O H C H 3 C O O C H 3 + H 2 O

M e th a n o l A c e t ic A c id M e th y l A c e t a te W a te r

M .W . 3 2 M .W .6 0 M .W . 7 4 M .W .1 8

REACTOR Methanol

Acetic acid

Methyl Acetate

Water to ETP

REACTOR Ethanol

Acetic acid

Ethyl Acetate

Water to ETP



116

Charge Acetone, Diethylacetamidomalonate, Potassium carbonate anhydrous

&FingolimodHClstage-1 in to reactor, stir & heat the content. After completion of

reaction, filter the reaction mass through Neutsch. Transfer the product filtrate ML in

to another reactor. Distil out solvent and then co-distil with hexane. Transfer the

product filtrate ML in to another reactor then charge purified water, stir & separate the

Aqueous Layer, organic layer dried with sodium sulphate, filter the reaction mass

through Neutsch. Transfer the product filtrate ML in to another reactor. Distil out

solvent and then unload the materialas FingolimodHCl stage-2.

Stage: 3

Charge Methylene Chloride, Fingolimod Hydrochloride Stage-2, Molecular Sieves

4A Pellets (Size 3mm) in to reactor, Stir the content of the reactor. Cool the content of

reactor, charge solution of Triethylsilane in Methylene Chloride into reactor.

Meanwhile prepare solution by mixing Titanium Tetrachloride in Methylene Chloride

and then charge into reactor, stir & cool the content of the reactor. After completion of

reaction, charge purified water in to reactor, stir & separate the Aq. Layer & organic

layer wash with purified water. Distil out solvent and co-distil out solvent with

Hexane, then again charge with Hexane & Ethyl acetate in to reaction mass, stir the

content. Distil out solvent and transfer the degas mass in to another reactor & prepare

the silica bed in hexane & load the degas mass, eluate with Ethyl acetate & hexane,

collect the fraction. Distil out solvent and check the LOD then unload the material as

FingolimodHCl stage-3.

Chemical reaction: Fingolimod hydrochloride, stage-1

CH3

O

Cl

Br

Formula Weight:190.32

Molecular Formula: C14H22

octylbenzene

Formula Weight: 157.39

Molecular Formula: C2H

2BrClO

bromoacetyl chloride

CH3

O

Br

HCl


Molecular Formula: C16

H23

BrO

2-bromo-1-(4-octylphenyl)ethanone Hydrochloric acid

Molecular Formula: HCl

Formula Weight:36.5

+

+



117

CH3

O

Br


Molecular Formula: C16H23BrO

2-bromo-1-(4-octylphenyl)ethanone

O

O

CH3

O

O

CH3

NH

O

CH3


Molecular Formula: C9H15NO5

diethyl (acetylamino)propanedioate

O

OCH3

OO

CH3

NH

O

CH3CH3

O

H Br

Formula Weight: 447.56Molecular Formula: C25H37NO6

Ketone melonic ester adduct (Fingolimod stage-2)

Formula Weight: 80.91Molecular Formula: HBr

hydrogen bromide

Fingolimod hydrochloride, stage-2

+

+

O

O

CH3O

O

CH3

NH

O

CH3

CH3

O



Ketone melonic ester adduct (Fingolimod stage-2)

Ti Cl

Cl

Cl

Cl


Molecular Formula: Cl4TiTitanium chloride

O

O

CH3O

O

CH3

NH

O

CH3

CH3



Fingolimod stage-3

OH2

TiO2

Chlorine(gas)Molecular Formula: 2Cl2Formula Weight: 141.82

Titanium dioxideMolecular Formula: TiO2


Water

Molecular Formula: H2O

Formula Weight: 18

+

Fingolimod hydrochloride, stage-3

+ +

+

2Cl2

+



118

Flow diagram:



119



120



121

TAMSULOSIN HYDROCHLORIDE


Stage: Final

Charge N,N-Dimethylformamide, Ethoxyphenoxy ethyl bromide, (R)-(-)-[2-

Aminopropyl]-2-methoxy benzene sulfonamide into reactor.Stir the content & heat it.

After reaction completion distil out N,N-Dimethylformamide completely under

vacuum. Charge Methylene chloride into reactor, adjust pH using Ammonia solution,

stir & cool the content. Settle the reaction mass and separate the lower product

enriched organic Layer in a clean HDPE drum.Keep the upper Aq. Layer in the

reactor. Charge Methylene chloride into reactor, stir the content.Stop stirring and

settle the reaction mass, separate the lower product enriched organic layer with

previously collected in HDPE drum.Unload the upper Aq. Layer in a clean HDPE

drum.Charges the combined product enriched organic layer followed by water into the

reactor and mix it. Stop stirring and settle the reaction mass. Separate the lower

product enriched organic Layer in a clean HDPE drum.Unload the upper Aq. Layer

with pre collected in HDPE drum. Charge the product enriched organic Layer in to

reactor. Distil out MDC completely then charge IPA in to reactor then distil out IPA.

Transfer the reaction mass in to another reactor, stir and cool the content of the reactor

&then centrifuge. Purification of wet cake using IPA and then acid base purification is

done. Charge IPA, wet cake in to reactor then add IPA & HCl. Stir and cool the

content &then centrifuge. Dry the product under vacuum tray dryer.

Chemical reaction:



122

H2O

+

HCl

Hydrochloric acid

MF:HCl

FW:36.5

Tamsulosin HCl, Stage-Final

NH2

CH3

S OO

NH2

O

CH3

5-[(2R)-2-aminopropyl]-2-methoxy- benzenesulfonamide

MF:C10

H16

N2O

3S

FW:244.31

O

CH3

O

Br

MF:C10H13BrO2

FW:245.12

Ethoxy phenoxy ethyl bromide

+

NH

CH3

S OO

NH2

O

CH3 O

CH3

O

MF:C20

H29

ClN2O

5S

FW:444.98

HBr

Hydrobromic acid

MF:HBr

FW:80.9

Tamsulosine Hydrochloride, Stage-Final

+ +

Water

MW:H2O

FW:18

HCl

+ H2O+

Water

MW:H2O

FW:18



123

Flow diagram:



124



125

CARBAMAZEPINE


Charge Methanol, Iminostilbenecarbonyl chloride, ammonia & purified water in to

reactor, stir & heat the content to desired temperature. After completion of

reactioncentrifuge the reaction mass followed by washing the wet cake with purified

water. Charge Acetone, Hyflo, wet cake, activated carbon in to another reactor & heat

the content up to desire temperature. Cool the reaction mass and filter it through

sparkler followed by micron. Transfer the filtrate in to another reactor, stir & cool the

content. Centrifuge the reaction mass followed washing of wet cake with acetone and

then lastly dry the product in fluid bed drier.



126

Chemical Reaction: Carbamezapine, stage-Final

OCl


Molecular Formula: C16H15ClO

Iminostilbene carbonyl chloride


Molecular Formula: NH4OH

Aq. ammonia

ONH2


Molecular Formula: C16H17NO

Carbamezapine, Stage-Final

HCl

Hydrochloric acid

Molecular Formula: HCl


NH4OH

H2O

Water

MF:H2OFW:18

+

++

Flow diagram:



127

NEBIVOLOL


STAGE-1

To stirred solution of 6-fluoro-3,4-dihydro-�-hydroxy]-2H-2-[1] benzopyran

Ethanamine and 6-fluoro-3,4-dihydro[tert-butyldimethylsilyl) oxy]-2H-2-[1]benzo

pyran Acetaldehyde in THF and methanol sodium cyanoborohydride is added and

stirred it for 14 h at rt. If reaction is incomplete SECOND lot of sodium

cyanoborohydride was added and stirred for 18 h at rt. Reaction was poured into

NaHCO3 and extracted with ethyl acetate. After evaporation solid wa found and

recrystalise further into DCM and methanol mixture.

STAGE-2

To a stirred solution of stage-5 in THF and methanol mixture was heated to 70°C in

acidic condition for one hrs. Sodium hydroxide solutions are added to reaction

mixture and extract it with ethyl acetate. The ml was concentrated to get the oil. Yield

97%.

STAGE-3

The oil was taken in methanol solution and mixed with 2N solution of HCl in diethyl

ether and allowed to stand at –20°C for crystallization. Later it was purified in

methanol. Yield 32 %.



128

Chemical Reaction:

O

F

OHC

OSi

CH 3

C H 3

C H 3

C H 3

CH 3

O

F

O H

N H 2

+

N a+

N BH 3THF/Methanol/EtOAc

6-f luoro-3,4-dihydro-[tert-buty ldim ethylsily l) oxy]-2H-2-[1]benzo pyran

Acetaldehyde

6-f luoro-3,4-dihydro-hydroxy]-2H - 2-[1] benzopyran E thanam ine

OF O H

N H

O

F

O Si

C H 3

CH 3

C H 3

C H 3

C H 3

6N HCl/Methanol

O

F

O H

N H O

F

O H

O

F

O H

N H O

F

O H

HCl

HClMethano l

Formula Weight = 324.46Formula Weight = 211.23

62.84




Nabivolo l H ydrochlo ride

+ NaOH + N BH 2

40 38.84

+ C l S i

C H 3

CH 3

C H 3

C H 3

C H 3

150.72

36.5

36.5

Stage-1

Stage-2

Stage-3



129

Flow Diagram



130

BRONOPOL (BP):


Charge methanol in Reactor then charge formaldehyde charge caustic lye slowly to the mixture.

This is maintained for 3 hours at 200C, after that charge bromine and maintain for 4 hours at

60oC, then methanol is recovered.

After total methanol recovery, charge water& Carbon this is then stir for 1 Hr. Then carbon is

filtered & water is distilled. The reaction mixture is chilled to 100C & centrifuge & dry. Ml is

sodium bromide solution & is collected separately.

Chemical Reaction:

CH 3NO2 + 2 HC HO HOCH2CH CH 2OH

N O2 NaO H (M W. 40)Br2(M W.1 60)N O2 HOCH 2 C - C H 2 OH + Na Br + H2O(M W. 61 ) ( MW. 60) (MW. 1 21 )

Br(MW. 200 ) (M W. 1 0 3 )



131

Flow diagram:

2-MERCAPTO BENZIMIDAZOLE:


Orthophenylene diamine (OPDA), water and Sodium sulphide (as catalyst) are charged into a

reactor and then carbon disulphide is slowly added to the reaction mass, which gives 2 Mercapto

Benzimidazole. This is then slightly heated to drive out the Hydrogen sulphide gas generated

which

is absorbed in a scrubber containing sodium hydroxide to give sodium hydrosulphide. The solids

are separated by filtration and the mother liquor is recycled in next charge. The product dried &

packed. The mother liquour after 20 charges cycles is sent to ETP.



132

Chemical Reaction:

Flow Diagram



133

TBHQ (Tertiary Butyl Hydroquinone)


• Charge Water, Phosphoric Acid, Toluene and Hydroquinone in the reactor.

• Slowly start addition of Tertiary Butanol (TBA) at 1020 C.

• After completion of reaction settle down the reaction mass.

• Collect the lower aqueous layer as phosphoric acid, which is going to be reuse in next

batch.

• Now do the filtration and get the filtrate as toluene (reuse) and get the Wet Cake.

• Take the wet cake in another reactor and add 20 times water at 950

C.

• After an hour cool down the mass and do the filtration.

• Get the filtrate as Di-Butyl Hydroquinone and take wet cake for centrifuge.

• Remove the water and go for drying and packing.

Chemical Reaction:

OHOH + CH3 C OH CH3 CH3 OHOH CH 3CH3 C CH3

+ H 2OH 3 PO4 To l ue n e1 02o C MW. 1 10 M W. 7 4 M W. 1 6 6 MW.1 8



134

Flow Diagram



135

ANNEXURE VII

DETAILS OF WATER CONSUMPTION

DETAILS OF WASTE WATER GENERATION

Note: * Zero Discharge Unit.

Domestic waste disposed off through soak pit/ septic tank.

Category As per CTE No. 70101

Water Consumption

(KL/Day)

For Proposed Project

Water Consumption

(KL/Day)

Domestic: 2.5 10

Industrial:

Process 3.0 102(fresh) +63(Recycle)

Boiler 2.0 40(Recycle)

Cooling 0.5 35

Washing 00 5(fresh)+25(recycle)

Other 2.0 5(recycle)

Total (Industrial) 7.5 132 (fresh)+133(recycle)

Total

Domestic + Industrial)

10.0 142 (fresh)+133(recycle)

Category As per CTE No. 70101

Waste Water

Generation (KL/Day)


Waste Water

Generation (KL/Day)

Domestic: 1.5 7

Industrial:

Process 00 155

Boiler 00 10

Cooling 00 5

Washing 00 3

Other 00 0

Total (Industrial) 00 * 173

Total

(Domestic + Industrial)

1.5 180



136

Water Balance:

Domestic

10

Soak Pit

7

Total water consumption

142(fresh) +133(recycle)

Process

102(fresh) +63(Recycle)

Boiler

20

Cooling

5(fresh)+ 25(recycle)

Gardening

5(recycle)

Effluent from

Process

155

Boiler blow

down

5

Cooling blow

down

3

Effluent Treatment Plant

173

RO Plant

173

RO Reject

70

RO Permeate

103

Evaporator

45

Condensate

30

Reject

10

To NCTL

25

Loss

10

Loss

15

Loss

25

• All quantity is in KL/Day

Washing

40 (recycle)

Loss

30

Loss

5



137

ANNEXURE-VIII

EXISTING EFFLUENT TREATMENT PLANT

There is no requirement of ETP.

PROPOSED EFFLUENT TREATMENT PLANT

Effluent coming from various streams is passed through Oil & Grease separator and

then collected in existing collection tank no.1. Then that effluent transfer to new ETP

equalization tank.

After that effluent transfer to neutralization tank where pH is maintained by dosing of

lime / alum. After ensuring pH, effluent is transferred to the primary clarifier tank.

Sludge settled at bottom of the clarifier is transferred to the sludge drying beds.

Over flow of primary clarifier effluent will goes in Aeration Tank, where continue air

is supplied by means of diffused Aeration System for biodegradation of organic

matters. Nutrients are added as per requirement. The overflow is goes to Secondary

Clarifier's, where settlement of biomass takes place. Some biomass is recycled in the

aeration tank by circulation pump and partly biomass wasted in to sludge drying bed

& sludge from decanter is stored in Hazardous Waste Storage Area, having

impervious layer and leachate collection system. Finally, stored hazardous waste

disposed off to government approved land filling site.

Over flow of secondary clarifier sent to intermediate tanks where sodium hypo

chloride added. Then effluent is passed through Activated carbon filter.

After filtration waste is transferred to final treated tank. Treated effluent from the final

collection tank is transferred to RO plant. RO permeate is reuse and rejected is sent to

evaporator. The evaporate permeate is used in cooling tower and gardening purpose.

PARTICULARS OF EFFLUENT TREATMENT PLANT

Sr.

No.

Description Size (L*W*D) Nos. Capacity

1 Equalization tank 4.5*6*4 1 108 m3

2 Neutralization tank 2.3*2.3*3 1 16 m3

3 Lime soln preparation tank 300 lit 1 0.3m3

4 Alum soln preparation tank 200 lit 1 0.2m3

5 Primary clarifier 2.5 M dia*2.5 1 51.3 m3

6 Aeration tank 7*6*4 1 168m3

7 Secondary clarifier 2.5 M dia*2.5 1 51.3 m3



138

8 Filter Foundation 6*3 1 18 m2

9 Storage tank 7*5*5 1 35m3

10 RO Shed 7*9 1 63m2

11 RO rejection tank 4.2*4.3*4 1 72.24m3

12 RO permeate tank 5.1*5.1*4 1 104.04m3

13 Sludge sump 2*2*3 1 12m3

14 Sludge drying bed 2*1.5*3 1 9m3

15 Evaporator 45m3

16 Condensate 30m3

17 Operator room 3*6 1 18m2

18 Hazardous Waste area 3*4 1 12m2



139

FIGURE -4

FLOW DIAGRAM OF ETP

Primary

Clarifier

Secondary

Clarifier

Carbon

Filter

column

Evaporator

RO

Column

RO Reject

RO

Permeate

Condensate Reject

Equalization

Tank

Neutralization

tank

Aeration Tank

Sludge Drying Bed TO TSDF

Sludge

Sludge

S

l

u

d

g

e

Activated Sludge

Storage

Tank

Effluent

Reuse



140

ANNEXURE-IX

DETAILS OF HAZARDOUS WASTE

Sr.

No.

Name of

Waste

Categ

ory

(As per

CTE No.

70101)

Quantity

for EC

Treatment & Disposal

1 Process

Organic

residue

28.1 0 77.32 Collection, storage for Onsite

Distillation

OR by

authorized other vendor OR Sale to

authorized recycler

2 Solvent

Residue

28.1 0 131.17 Collection, storage, transportation &

disposal by incineration at CHWI or

send for co‐processing in cement

industries

3 Process

Inorganic

Residue

28.1 0 25.85 Sent to TSDF

4 Spent

charcoal and

hyflo



send for co‐ processing in cement

industries

5 Spent

Organic



send for co‐ processing in cement

industries

6 Spent

Inorganic

28.2 0 145.00

Sent to TSDF

7 Spent

Solvents



send for co‐processing in cement

industries

8 ETP Sludge 34.3 0 5 Collection, storage, transportation &

disposal to TSDF

9 Discarded

Container/

Bags/liner

33.3 40 Nos.

200Nos.

50 Nos.

300 Nos.

After detoxification sent

to Authorized agencies

10 Used Oil 5.1 0.012 MT 1KL/Mon

th

After detoxification sent

to Authorized agencies

11 Spent Mother

Liquor

28. 4 0 1874.63 Collection, storage, onsite treatment in

MEE Dryer & incineration OR

transportation & disposal by

incineration at CHWI or send

for co‐ processing in cement industries

12 Process

Waste

34.3 8.334 0 Sent to TSDF site of M/s. BEIL,

Ankleshwar

13 Gypsum

Sludge

-- 10 0 Sent to TSDF site of M/s. BEIL,

Ankleshwar OR Brick manufacturer

14 Briquette -- 18.334 10 Sold to Brick



141

Sr.

No.

Name of

Waste

Categ

ory

(As per

CTE No.

70101)

Quantity

for EC

Treatment & Disposal

Ash manufactures



142

ANNEXURE X

ENERGY AND FUEL CONSUMPTION DETAILS

Sr.

No.

Particulars Requirement Remark

Electricity

Electricity 125KVA DGVCL

Fuel

Bio-Coal 300 tonne From local supply

• There is no change in energy and fuel consumption.



143

ANNEXURE XI

FLUE GAS EMISSION

PROCESS EMISSION

Sr.

No.

Stack

Attached

To

Stack

Height

Fuel

Consumptio

n

Air

Pollution

Control

System

Type

of

Emission

Permissible

Limit

As per CTE-70101

1.

IBR

Boiler

( 2TPH)

11 m

Wood:- 700

Kg/Day Or

Baggase:-

700Kg/Day

Multi

Cyclone +

Bag Filter

+ Water

Scrubber

PM

SO2

NOx

150mg/NM3

100 PPM

50 PPM


1.

IBR

Boiler

( 2TPH)

11 m

Wood:- 700

Kg/Day Or

Baggase:-

700Kg/Day

Multi

Cyclone +

Bag Filter

+ Water

Scrubber

PM

SO2

NOx

150mg/NM3

100 PPM

50 PPM

Sr.

No.

Stack

Attached

To

Stack

Height

(m)

Stack

Diamete

r

(m)

Air Pollution

Control System

Type of

Emission

Permissible

Limit

1.

Reactor

Vessel

25 0.5 Water Scrubber +

Alkali Scrubber

HBr

SO2

HCl

20 mg/Nm3

40 mg/Nm3

20 mg/Nm3

2. Reactor

Vessel

25 0.5 ---- CO2

H2O

• This is no any process gas emission in due to existing product.



144

DETAILS OF AIR POLLUTION CONTROL SYSTEM

Working:

As the contaminated fumes with particles, coming from bag filter and goes to

water scrubber. Water is sprayed from the top of the nozzle, which washes the large

particle from the contaminated fumes and settles down to the bottom.

Upper water from the bottom of the scrubber is circulating through the pump

to spraying nozzle. Solid particle is accumulating at the bottom of the scrubber which

is giving to the BEIL.



145

ANNEXURE XII

PROCESS DESCRIPTION

A solvent recovery system comprises of two stage heat exchangers. Cooling

tower water is circulated in primary heat exchanger and in secondary heat

exchanger chilled water circulation is done. The uncondensed solvent after the

secondary heat exchanger will be diverted to water scrubber the traces of

solvent will get dissolved in water. On getting saturation, the solvent mix

water will be subjected for recovery of solvent (if feasible) and/or water will

be diverted to ETP plant for further treatment the process will ensure no VOC

emission from solvent recovery system.

FIGURE: 3

SOLVENT RECOVERY SYSTEM

Reactor

Primary

Condenser

Cooling Tower Line

Secondary

Condenser

Chilled Water

Circulation Spray

Water Tank

Receiver



146

ANNEXURE XV

LIST OF HAZARDOUS CHEMICAL

Sr. No. Raw Material

1 1,1-dimethyl ethyl -6-(2-aminoethyl)

2 4-Fluoro -2-methyl-1-oxopropyl

3 Cyclohexane

4 Iso propyl alcohol(IPA)

5 Hydrochloric acid

6 Acetonitrile

7 Sodium hydroxide

8 Calcium acetate

9 Hyflow

10 4(S)-4-hydroxy-6-sulfonamide dioxide

11 Methane sulfonic anhydride

12 Ethyl amine

13 Aq.Ammonia

14 Pyridine

15 Tetra Hydrofuran(THF)

16 Sodium bicarbonate

17 Carbon

18 2-(5-bromo-2-methyl benzul)-5-(4-flurophenyl)thiophene

19 Silyl D-gloconolactone

20 Methanol

21 Acetone

22 Potassium carbonate

23 2,3-di-o-acetyl-5-deoxy-5-fluorocytidine

24 n-Pentyl Chloroformate

25 Methylene Chloride(MDC)

26 Ethyl Acetate

27 Activated Carbon

28 RS-a-Sulfophenyl acetic acid

29 (S) –a- Methyl benzyl amine

30 1-Hydroxy benzotriazole

31 Methane sulphonyl chloride

32 Hexane

33 7-Amino cephalosporic acid

34 Boron trifluride etherate

35 Tert-butyl acetate

36 Zinc chloride

37 Triethyl amine



147

38 Di isopropyl ether(DiIPE)

39 Pyridine-4-carboxamide

40 Sodium iodide

41 Dimethyl formamine

42 Ethanol

43 Sodium acetate

44 3-[(1-Methyl-2-{[4-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)-

phenylamino]-methyl)-1Hbenzoimidazole-5-carbonyl)-pyridin-2-yl

amino]-

propionic acidethyl ester

45 P-toluene sulphonic acid

46 Acetic acid

47 Hexa chlorofomate

48 �-(dimethylamino) benzenepropanol

49 1-fluoronaphthalene

50 Dimethyl sulfoxide(DMSO)

51 n-Propanol

52 (3R,3as,4aR)-hexahydrofuro[2,3-b]furan-3-ol

53 4-Amino-N-(2R,3S)(3-amino-2-hydroxy-4-phenyl-butyl)-N-isobutyl

benzenesulfonamide

54 Disucinimidyl carbonate

55 Sulphuric acid

56 2-Methyl2-Butanol

57 2-[3-Methyl-4-(2,2,2-trifluoro-ethoxy)-pyridin-2-ylmethanesulfinyl]-

1H-benzoimidazole

58 L (+) Mandelic acid

59 Diethyl tartarate

60 Titanium isopropoxide

61 Triethyl amine

62 Aloe emodine

63 Sodium dichromate dihydrate

64 Propionic anhydride

65 Toluene

66 Acetic anhydride

67 N-Methyl pyrrolidone

68 Celite

69 (±)-Trans-5,6-dihydro-4H-4-Ethyl amino-6-methylthieno[2,3-

b]thiopyran-2-sulfonamide-7,7-dioxide

70 n-Butanol

71 (-)Di-para-toluoyl-Ltartaric acid monohydrate

72 Intermediate-I



148

73 Intermediate-II

74 n-butyl lithium in THF

75 Triethyl tin hydride

76 Trifluro borate-etharate

77 5-Methoxy-2-[[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]thio]-1H-

benzimidazole

78 Hydrogen Peroxide

79 Vanadium acetyl acetonate

80 Ammonia liquor

81 Magnesium Chloride

82 (S)-(-)-1,1-Bi-2-Naphthol

83 2-butyl-1,3-diazaspiro[4,4]non-1-ene-4-one hydrochloride

84 5-[4'-(bromomethyl) biphenyl-2-yl]-1-trityl-1Htetrazole

85 Methanolic HCl

86 Methylene Methylene

87 30% sodiumhydroxide lye

88 2-[2-[3(S)-[3-[2-(7-Chloro-2-quinolinyl)-ethenyl]phenyl]-3-

hydroxypropyl]phenyl-2-propanol

89 2-[1-(Sulfonyl methyl)cyclopropyl]acetic acid

90 N,N-Diisopropylethylamine

91 N-{4-[4-(4-Hydroxyphenyl)-piperazin-1-yl]-phenyl}-carbamic acid

phenyl ester

92 Formic acid N'-(2-benzyloxy-1-ethyl-propyl)-hydrazide

93 (5R-cis)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-

ylmethyl)tetrahydrofuran-3-methanol tosylate

94 methanol tosylate

95 2,3,4,6,7,8,9,10-Octahydro pyrimido[1,2-a]azepine

96 Formic acid

97 Dimethyl Sulfoxide

98 Palladium

99 Dibenzo-(1,4)-thiazepine-11(10H)-one

100 2-(2-(piperazin-1-yl)ethoxy)ethanol

101 Thionyl chloride

102 3- Pyridyl Acetic Acid

103 Diethyl carbonate

104 Methane sulfonic Acid

105 1H-Benzimidazole-2npropyl-4-methyl-6-(1-methyl benzimidazole-2yl]

106 4-methyl-(bromomethyl) bi phenyl carboxylate

107 Methyl Iso Butyl Ketone (MIBK)

108 5-{4-[4-(5-Cyano-1H-indol-3-yl)-butyl]-piperazin-1-yl}-benzofuran-2-

carboxylicacid methyl ester



149

109 PHBA

110 MONO ETHYLENE GLYCOL

111 2-METHOXY-5-SULPHOMYL METHYL BENZOATE

112 S-1-ETHYL-5-AMINOMETHYL PYROLLIDINE

113 HEXA METHYL DI AMINE

114 SODIUM DI CYNAMIDE

115 TRI ETHYL AMINE

116 SODIUM HYDROXIDE FLAKES

117 PCA HCL

118 1-H-1,2,4-trizole

119 Epoxy comound

120 2-chloro 2,3 dimethoxy pyridine

121 5-dithiomethoxymenzimidazole

122 TEBA

123 sodium hypochlorite

124 sodium thiosulphate soln.

125 IPE

126 2-methoxy-ethyl-(3-nitro benzylidine)acetoacetate

127 3-amino crotonic acid cinnamyl ester

128 Benzo Pyran Acetaldehyde

129 Benzo Pyran ethelamine

130 Sodium Cyano borohydried

131 diethyl Ether

132 4-Methyl 2-Nitro Anisidine

133 Sodium hydro Sulfide

134 Carbon disulfide

135 Benzyl amine DPTT

136 Cerric Ammonium nitrate

137 NaBH4

138 4,6‐Dichloro‐5‐(2‐Methoxyphenoxy)‐2,2‐Bipysimidine

139 4‐Tert‐Butylbenzene Sulfonamide

140 Sodium Tert Butoxide

141 (4‐4‐Aminophenyl)‐morpholin‐3‐one

142 Glycidyl Phthalimide

143 4‐Dimethylaminopyridine(DMAP)

144 CDI

145 5‐Chlorothiophene‐2‐cacoxylic acid

146 Oxalyl Chloride

147 Aq. Methyl Amine

148 KSM

149 Isobutyl Bromide



150

150 Ammonium Hydroxide. HCl

151 2‐(7‐methoxy‐1‐napthyl)Acetonitrile/ Agomelatine

152 Hydrogen Gas

153 Isopropyl Alcohal HCl

154 S(+)-2 amino butyramide hydrochloride

155 4-chloro butyryl chloride

156 Nitro Methane

157 Formaldehyde

158 Bromine

159 ODPA

160 Hydroquinone

161 Tertiary Butanol (TBA)

162 Iminostilbenecarbonyl chloride

163 Octylbenzene

164 Aluminium chloride

165 Bromoacetyl bromide

166 Diethylacetamido malonate

167 Triethylsilane

168 TiCCl4

169 Maleic acid

170 Ethyl acetate for washing

171 N,N-Dimethylacetamide

172 4-(Dimethylamino)pyridine

173 1-hydroxybenzotriazole

174 Dimethylformamide

175 Ethoxy phenoxy ethyl bromide

176 Cetyl Chloride

177 Pyridine

178 Methyl ethyl ketone

179 Lauryl Chloride

180 Acefilline

181 Ambroxol Base

182 Anisol

183 3,5 Dribromo Acetophenone

184 Nicotonic acid

185 Fresh Benzene

186 Chlorine gas

187 Furfuraldehyde

188 2,3 Dichloro Aniline

189 Fresh orthoxylene

190 Bis Salt



191 Hydrazine Hydrate

192 Meta Di Chloro benzene

193 Imidazole

194 ISO Nicotinamide

195 Paraformaldehyde

196 DMA HCl

197 Acetophenone

198 Catechol



Hydrazine Hydrate

Meta Di Chloro benzene

ISO Nicotinamide

Paraformaldehyde


151



152

ANNEXURE XIV

CTE



153



154

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ANNEXURE I TERMS OF REFERENCE - …environmentclearance.nic.in/writereaddata/FormB/TOR/Additional... · M/s. PRANSHAV HEALTH CARE, JHAGADIA, BHARUCH Jyoti Om Chemical Research Centre