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LIST OF PRODUCTS
BULK DRUGS
Sl. No Name of the product Production TPM
1. Carvedilol phosphate 2.50
2. Citalopram Hydrobromide 10.00
3. Closantel sodium 5.00
4. Esomeprazole magnesium trihydrate 1.50
5. Fexofinadine hydrochloride 2.00
6. Fosfomycin trometamol 3.00
7. Gaba-pentin 3.00
8. Itraconozole 2.00
9. Lansoprazole 3.00
10. Lornoxicam 4.00
11. Montelukast sodium 3.00
12. Omeprazole 5.00
13. Ondansetron 3.00
14. Oxyclozanide 5.00
15. Ritonavir 3.00
16. Rosuvastatin calcium 3.00
17. Setraline hydrochloride 2.00
18. Sparfloxacin 2.00
19. Terbinafine hydrochloride 3.00
Total 65.00
INTERMEDIATES
Sl. No Name of the product Production TPM
1 Tri Chloro Salisylic Acid 3.00 2 5-AminO-2-Hydroxy Benzoic acid 2.00 3 5-Amino-2-dibenzylamino-1,6-diphenyl-hex-4-en-3-one 2.00 4 2-Amino-6-chloro-3-nitro pyridine 3.00 5 4-Chloro butyryl chloride 3.00
CHEMICALS
Sl.No Name of the product Production TPM
1 Tributyl Tin chloride 90 2 L-Menthol 90 3 Dicyclo Hexylcarbomidiimide 90
SOLVENT RECOVERY
Sl.No Name of the product Production
TPM1 All solvents 450
Industry proposes to produce
• 2.0 TPD either from bulk drug group or intermediate group • 3.0 TPD from chemicals group • 15.0 TPD solvent recovery
CARVEDILOL PHOSPHATE
Carvedilol Phosphate can be manufactured in four stages.
Stage-1:
1-(2-bromo ethoxy)-2-methoxy benzene and benzyl amine reacts together in the presence of toluene
solvent medium forms stage-1 compound.
O
OBr
1-(2-Bromo-ethoxy)-2-methoxy-benzene
C9H11BrO2Mol. Wt.: 231.1
NH2
Benzylamine
+
C7H9NMol. Wt.: 107
O
ONH
Stage-1
+HBr
Hydrobromic acidMol.Wt.:81
C16H19NO2Mol. Wt.: 257
Toluene
Stage-2:
Statge-1 compound reacts with 2-chloro ethyl-oxirane in the presence of methanol solvent medium forms
the stag-2 compound.
O
ONH
Stage-1C16H19NO2
Mol. Wt.: 257
OCl+
2-Chloromethyl-oxiraneC3H5ClO
Mol. Wt.: 92
Methanol
Stage-2
O
ONCl
OH
C19H24ClNO3Mol. Wt.: 349.8
Stage-3:
Stage-2 compound reacts with 9H-carbazol-4-ol in the presence of potassium carbonate forms the
stage-3 compound.
Stage-2
O
ONCl
OH
C19H24ClNO3Mol. Wt.: 349.8
NH
OH
+
9H-Carbazol-4-olC12H9NO
Mol. Wt.: 183
O
ONOH
NH
O
C31H32N2O4Mol. Wt.: 496.6
+HCl
Hydrochloricacid
Stage-3
Mol.Wt.:36.5
K2CO3
Stage-4:
Stage-3 compound undergoes reduction in the presence of H2; Pd/C forms the carvedilol free base.
O
ONOH
NH
O
C31H32N2O4Mol. Wt.: 496.6
Stage-3
H2, Pd/C
C24H26N2O4Mol. Wt.: 406.5
Carvedilol free base
+
CH3
TolueneC7H8
Mol. Wt.: 92
O
ONH
OH
NH
O
+ H2
Hydrogen
Mol. Wt.: 2
Stage-5:
Carvedilol free base reacts with phosphoric acid and water forms carvedilol phosphate. The reaction
proceeds as per the below equation.
O
ONHOH
NH
O
C24H26N2O4Mol. Wt.: 406.5
Carvedilol free base Phosphoric acid
P
O
OH
OH
OH+
H3O4PMol. Wt.: 98
+ 1/2 H2O
Water
Mol.Wt.: 9
O
OH
NHO
OCH3
. H3PO4 .1/2 H2O
Carvedilol phosphateC25H30NO8P
Mol. Wt.: 513.5
H2O
FLOW CHART OF CARVEDILOL PHOSPHATE
Layer Seperator
Reactor
Stage-1
1-(2-bromo ethoxy)-2-methoxy benzenebenzyl amine
Toluene
Centrifuge
Spent toluene to recovery
Forms hydrobromic acid
Stage-1
Reactor
Stage-2
stage-1 product2-chloro ethyl-oxirane
Methanol
Centrifuge
Spent methanol to recovery
Stage-2
Stage-29H-carbazol-4-ol
Potassium carbonateReactor
Stage-3
Centrifuge
Layerseparation
Stage-3
HCl gas to scrubbing
Stage-3 comoundH2, Pd/C
Reactor
Stage-4
Centrifuge
Layerseparation
Toluene to recovery
Cavedilol free base
Carvedilol free basePhosphoric acid
WaterReactor
Centrifuge Waste water to recovery
Stage-5
Pharma
Distillation
CITALOPRAM HYDROBROMIDE
The product is manufactured in three stages.
Stage-1:
4-[4-Dimethylamino-1-(4-fluoro-phenyl)-1-hydroxy-butyl]-3-hydroxymethyl-benzonitrile on Cyclisation in
presence of Phosphoric acid and Ammonia solution produces stages-1 product.
F
NCOH
OH N
CH3
CH3
4-[4-Dimethylamino-1-(4-fluoro-phenyl)-1-hydroxy-butyl]-3-hydroxymethyl-benzonitrile
C20H23FN2O2Mol. Wt.: 342
Phosphoric acidLiq.Ammonia,Toluene O
F
NC
N
CH3
CH3
.H2O
Stage-1C20H22FN2O
Mol. Wt.: 324.4
+
Water
Mol. Wt.: 18 Stage-2: Citalopram Hydro bromide is produced when stage-1 compound reacts with Hydrobromic acid . Isopropyl
alcohol, Carbon and Di isopropyl ether is used in the process.
O
F
NC
N
CH3
CH3
Stage-1C20H22FN2O
Mol. Wt.: 324.4
+ HBrIPA
O
F
NC
N
CH3
CH3
HBr
Citalopram HydrobromideC20H22BrFN2OMol. Wt.: 405.3
BrHMol. Wt.: 80.9
Hydro bromicacid
FLOW CHART OF CITALOPRAM HYDROBROMIDE
Stage-1
4-[4-Dimethylamino-1-(4-fluoro-phenyl)-1-hydroxy-butyl]-3-hydroxymethyl-benzonitrile
Phosphoric acidLiq.Ammonia,Toluene
Water
Reactor
Centrifuge Ammonium phosphate saltsolution for sale
Stage-1
Toluene to recovery
Stage-2:Pharma
Reactor
Centrifuge
Stage-Pharma
Stage-1Hydrobromic acidDi Isopropyl etherIospropyl alcohol
Spent solvent to recovery
Di Isopropyl ether
CLOSANTEL SODIUM
The product is manufactured in three stages.
Stage-1:
Step-A:
Sodium bicarbonate and Sodium sulphide react together in presence of water to produce Sodium
hydrogen sulphide
Sodiumbicarbonate
Water
Sodiumhydrogensulphide
Mol. Wt.: 84 Mol. Wt.: 56
NaHCO3 Na2S+
Sodiumsulphide
Mol.Wt.:78
NaHS + Na2CO3
SodiumCarbonate
Mol.Wt.:106
Step-B:
This mass is made to react with 1-chloro-3-methyl-5-nitro benzene and p-Chloro Benzyl cyanide in
presence of toluene solvent medium and water to produce the stage-1 compound.
ClN
C8H6ClNMol. Wt.: 151.6
+NaHS
Cl
H2N
Cl
CH3
CN
Stage-1
Toluene
1-Chloro-3-methyl-5-nitro-benzene
C7H6ClNO2Mol. Wt.: 171.6
parachlorobenzyl cyanide
C15H12Cl2N2Mol. Wt.: 291.2
+ O2
Oxygen
N+
–O
O
Cl
CH3
O2Mol. Wt.: 32
Stage-2:
Stage-1 on reaction with 2-Hydroxy-3, 5-diiodo-benzoicacid by means of phosphorous trichloride in
presence of toluene solvent medium and water to form the stage-2 compound
Cl
H2N
Cl
CH3
CN
Stage-1C15H12Cl2N2
Mol. Wt.: 291.2
+
2-Hydroxy-3,5-diiodo-benzoic acid
C7H4I2O3Mol. Wt.: 389.9
Toluene/PCl3Water
Closantel
+H2O
Water
Mol. Wt.: 18
Cl
Cl
CH3
CH
COHI
I
NH
O N
OH
I
I
O
OH
C22H14Cl2I2N2O2Mol. Wt.: 663.1
Stage-3:
Stage-2 compound with Formic acid and Sodium Hydroxide in Water and Acetone
Closantel
Cl
Cl
CH3
CH
COHI
I
NH
O N
C22H14Cl2I2N2O2Mol. Wt.: 663.1
+
O
OH
Formic acidCH2O2
Mol. Wt.: 46
WaterAcetone
Na+
O
NHO
O-
I
I
OH
CH3
N
Cl
Cl
C23H15Cl2I2N2NaO4Mol. Wt.: 731.1
Closantel SodiumWater
Mol. Wt.: 18
H2O +
+ NaOH
SodiumHydroxide
Mol. Wt.: 40
FLOW CHART OF CLOSANTEL SODIUM
Stage-1Sodiumbicarbonate
Sodium SulphideWater
Reactor
Reactor
1-chloro3-methyl-2-nitro benzeneparachlorobenzyl cyanideSodium Hydrogen Sulfide
Toluene
Centrifuge
Inorganic salt solution to waste
Stage-1
Tolouene to recoveryO2 gas to scrubbing
Stage-2:
Stage-12-Hydroxy-3,5-diiodo-benzoic acid
ToluenePhosphorus tri chloride
water
Reactor
Centrifuge Inorganic salt solution to waste
Stage-2
Toluene to recovery
Stage-3:Closantel
Formic acidSodium Hydroxide
WaterAcetone
Reactor
Centrifuge
Acetone to recovery
Water to waste
Final compound
ESOMEPRAZOLE MAGNESIUM TRIHYDRATE
The product is produced in two stages.
Stage-1:
5-Methoxy-2-(4-methoxy-3, 5-dimethyl-pyridin-2-yl-methyl sulfanyl)-1H-benzoimidazole reacts with
cumene hydro peroxide and potassium Hydroxide by means of titanium isopropoxide in presence of
Methylene dichloride solvent medium to form the stage-1 product.
+
cumene hydroperoxideC9H12O2
Mol. Wt.: 152.2
Titaniumisoperoxide
KOH
O
SNO
NN
CH3
OCH3
Esomeprazole Potassium
C17H19N3O2SMol. Wt.: 329.4
Phenyl-acetic acidC8H8O2
Mol. Wt.: 136.2
+
K
H2O +
5-Methoxy-2-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethylsulfanyl)-1H-benzoimidazole
O
OH
WaterMol.Wt.:18
N
NHS
N
O O
C17H18KN3O3SMol. Wt.: 383.5
+
OO H
Mol. Wt.: 56.1
PotassiumHydroxide
MDC
Stage-2:
Stage-1 compound on reaction with Magnesium Chloride solution in presence of acetone solvent medium
to form the final compound
Esomeprazole PotassiumC34H36N6O6S2K2
Mol. Wt.: 767
+ Mg.Cl2
MagnesiumChloride
Mol. Wt.: 95
3 H2O2
OS
N
NN
Mg
+2 KCl
Esomeprazole Magnesium trihydratePotassium Chloride
O
SNO
N
NCH3
OCH3
K
OS
N
NN
O
O
O
O
H2O H2O H2O
Cl2K2Mol. Wt.: 149
C34H42MgN6O9S2Mol. Wt.: 767.2
+
H6O3Mol. Wt.: 54
Water
Acetone
FLOW CHART OF ESOMEPRAZOLE MAGNESIUM TRIHYDRATE
Centrifuge
Stage-1
Stage-1:
Reactor
5-Methoxy-2-(4-methoxy-3, 5-dimethyl-pyridin-2-yl-methyl sulfanyl)-1H-benzoimidazole
Cumene hydro peroxidePotassium hydroxide
Titanium isopropoxideMethylene Dichloride
Solvent Mls
Layerseparator
Phenyl acetic acid
Water to waste
Reactor
Centrifuge
Acetone to recovery
Pharma
Stage-2:
Stage-1Magnesium Chloride
WaterAcetone
Inorganic salt solution to waste
FEXOFINADINE HYDROCHLORIDE
The product is produced in three stages.
Stage-1:
2-[4-(4-Chloro-butyryl)-phenyl]-2-methyl-propionic acid methyl ester undergoes condensation with
Azacyclonol and Sodium Bicarbonate by means of Methyl isobutyl ketone in presence of Ethyl alcohol
solvent medium to form the stage-1 compound.
+ + NaHCO3
SodiumBicaronate
Mol. Wt.: 84
MIBKEtOH
Stage-1
AzacyclonolC18H21NO
Mol. Wt.: 267.4
C33H39NO4Mol. Wt.: 513.7
C15H19ClO3Mol. Wt.: 282.8
OH
NH
+ NaCl
Sodium ChlorideMol.Wt.:58.5
+CO2
Carbon dioxide
Mol.Wt.:44
+H2O
Water
Mol.Wt.:18
2-[4-(4-Chloro-butyryl)-phenyl]-2-methyl-propionic acid methyl ester
OOO
Cl
OH
N
C+
CH3CH3
O
O
O CH3
Stage-2:
Stage-2 compound is produced when stage-1 compound, Sodium hydroxide and Acetic acid react together
with water in presence of Methanol solvent medium.
Stage-1
OH
N
CH3 CH3
O
O
O
+Methanol
Stage-2
NaOH
SodiumHydroxideMol.Wt.:40
+
O
HO
Acetic acidC2H4O2
Mol. Wt.: 60
+ H2O
Water
Mol.Wt.:18
OH
N
CH3 CH3
O
O
OH
C32H37NO4Mol. Wt.: 499.6
++ + Na+
O
O-
Sodium acetateC2H3NaO2
Mol. Wt.: 82
OH
MethanolCH4O
Mol. Wt.: 32Mol.Wt.:18
C33H39NO4Mol. Wt.: 513.7
Hydrogen
H2O
Stage-3:
Stage-2 compound is treated with Hydrochloric acid in presence of isopropyl alcohol solvent medium to
produce the pharma.
Stage-2
OH
N
CH3 CH3
O
O
OH
C32H37NO4Mol. Wt.: 499.6
+ HCl
Hydrochloricacid
Mol. Wt.: 36.5
IPA
.HCl
Fexofenadine HCl
OH
N
CH3 CH3
O
O
OH
C32H38ClNO4Mol. Wt.: 536
FLOW CHART OF FEXOFINADINE HYDROCHLORIDE
Reactor
Centrifuge
stage-1:
2-[4-(4-Chloro-butyryl)-phenyl]-2-methyl-propionic acid methyl ester
AzacyclonolSodium bicarbonate
Methyl isobutyl ketoneEthyl alcohol
Ethanol to recovery &CO2 gas to scrubbing
Inorganic salt solution to waste
Stage-1
Stage-1 productSodium hydroxide
Acetic acidWater
Methanol
Reactor
Centrifuge
Stage-2:
Methanol to recovery
Waste water
Stage-2
Stage-3:
Stage-2 productHydrochloric acid
IsopropanolReactor
Centrifuge
Solvent recovery
Final product
FOSFOMYCIN TROMETAMOL
The product is produced in two stages.
Stage-1:
Fosfomycin phenyl ammonium salt on coupling with Trometamol produces stage-1 compound. Ethanol is the solvent used.
Reaction proceeds as per the below equation.
NH2
OHOH
OH
TrometamolC7H18NO7P
Mol. Wt.: 259.2
O
CH3 PO
OHOH .
Fosfomycin phenyl ammonium salt
+ NH2
OHOH
OH
C4H11NO3Mol. Wt.: 121
Ethanol
Bis-Fosfomycin trometamol disaltC11H29N2O10PMol. Wt.:380.2
NH2
OHOH
OHO
CH3 PO
OHOH2
Stage-2:
Stage-1 on reaction with Fosfomycin in presence of methane sulfonic acid produces the final compound. The reaction
proceeds as per the below equation.
Bis-Fosfomycin trometamol disaltC11H29N2O10PMol. Wt.:380.2
NH2
OHOH
OHO
CH3 PO
OHOH2
O
CH3P
O
OHOH+
C3H7O4PMol. Wt.: 138.1
Fosfomycin
methane sulfonic acid
O
CH3 PO
OHOH
NH2
OHOH
OH
2
C11H29N2O10PMol. Wt.:518
Fosfomycin trometamol
FLOW CHART OF FOSFOMYCIN TROMETAMOL
Stage-1
TrometamolFosfomycin Phenyl ammonium salt
EthanolReactor
Centrifuge
Ethanol to reuse
Stage-1
Stage-2
Reactor
Centrifuge
Methane sulfonic acid to reuse
Stage-2:Pharma
Stage-1Fosfomycin
Methane sulfonic acid
GABA-PENTIN
The compound can be prepared in three stages.
Stage-1:
The cyclohexane-1, 1-diacetic acid mono amide is treated with sodium hypochlorite by means of Water in
presence of Di chloro methane solvent medium to get Stage-1 compound.
Cyclohexane-1, 1-diacetic Acid monoamide
+
sodiumhypochlorite
WaterMDC
+CO2
Carbondioxide
Mol. Wt.: 44
+ NaCl
Sodium chloride
Mol. Wt.: 58.5
+H2O
Water
Mol. Wt.:18
NH2
NH2
C10H18N2O2Mol. Wt.: 198.3
Na+
Cl O-
ClNaOMol. Wt.: 74.4
NH
O
C9H15NOMol. Wt.: 153
2-Aza-spiro[4.5]decan-3-one
OO
Stage-2:
2-Azaspiro [4, 5] decan-3-one on acid hydrolysis with concentrated hydrochloric acid in presence of
water gives Gaba-Pentin hydrochloride.
NH
O
C9H15NOMol. Wt.: 153
2-Aza-spiro[4.5]decan-3-one
+ HCl
Hydrochloricacid
Mol. Wt.: 36.5
Water O
OH
NH2
(1-Aminomethyl-cyclohexyl)-acetic acid
.HCl
C9H18ClNO2Mol. Wt.: 207.7
Stage-3:
Gaba-pentin hydrochloride on neutralization with sodium hydroxide in presence of water gives Gaba-
pentin. Finally product is purified with Carbon
O
OH
NH2
(1-Aminomethyl-cyclohexyl)-acetic acid
.HCl
C9H18ClNO2Mol. Wt.: 207.7
+ NaOH
Sodium hydroxideMol. Wt.: 40
Water
OOH
NH2
(1-Aminomethyl-cyclohexyl)-acetic acid
+ NaCl + H2O
Sodiumchloride
Mol. Wt.: 58.5
Water
Mol. Wt.: 18C9H17NO2
Mol. Wt.: 171.2
FLOW CHART OF GABA-PENTIN
Stage-1Cyclohexane-1,1-diaceticacid monoamide
sodium hypochloriteWaterMDC
Reactor
Centrifuge
CO2 gas to scrubbingMDC to recovery
Inorganic salt solution
Stage-1
Stage-2
Stage-1HCl
WaterReactor
Centrifuge
Stage-2
Water to waste
Stage-3
Stage-2Sod.Hydroxide
CarbonWater
Reactor
Centrifuge Inorganic slt solution to waste
Pharma
ITRACONOZOLE
The product can be manufactured in ten stages.
Stage-1:
p- Methoxy phenyl piperazine HCl is condensed with p-Nitro chloro benzene in presence of DMSO solvent medium forms the stage-1 compound.
N NHOH
Cl
p-methoxy phenyl piperazine HClC11H17ClN2O
Mol. Wt.: 228.7
N+
O-
Cl
p-nitro chloro benzene
+
C6H4ClNO2Mol. Wt.: 157.6
DMSO
N N
O
CH3
N+
O–
O
C17H19N3O3Mol. Wt.: 313
Stage-1
2 HCl
Hydrochloric acid
+
Cl2H2Mol. Wt.: 73
O
Stage-2:
Stage-1 compound is reduced with Nickel and palladium charcoal in the presence of methanol solvent medium forms the stage-2 compound.
N N
O
CH3
N+
O–
O
C17H19N3O3Mol. Wt.: 313
Stage-1
3 H2+
HydrogenMol. Wt.: 6
Ni , Pd/C
Methanol
N N
NH2
2 H2O
Stage-2C17H21N3OMol. Wt.: 283.4
+
H4O2Mol. Wt.: 36
WaterO
CH3
Stage-3:
Stage-2 compound on condensation with Phenyl chloro acetate in presence of toluene solvent medium produces stage-3 compound.
N N
O NH2
Stage-2C17H21N3O
Mol. Wt.: 283.4
phenyl chloro acetate
+Toluene
N NOH3C
NH
O
O
Cl
C O
O
C25H26N2O3Mol. Wt.: 402.5
Stage-3
+H Cl
Hydrochloricacid
Mol.Wt.:36.5
C7H5ClO2Mol. Wt.: 156.6
CH3
Stage-4:
Stage-3 product on doing reduction with Hydrazine hydrate in presence of 1, 4-dioxane at high temperatures forms the stage-4 compound.
N NO
H3C
NH
C O
O
C25H26N2O3Mol. Wt.: 402.5
Stage-3
+NH2
NH2HO
H
Hydrazine hydrateH6N2O
Mol. Wt.: 50.1
N NO NH
C O
NH
NH2
Stage-4C19H24N4O2Mol. Wt.: 340
OH
Phenol
+
C6H6OMol. Wt.: 94
+HO
H
WaterMol.Wt.:18
1,4-Dioxane
Stage-5:
Stage-4 compound on cyclization with formanidine gives Stage-5 compound in the presence of Acetic acid forms the stage-5 compound.
N NO
H3C
NH
C O
NH
NH2Stage-4C19H24N4O2Mol. Wt.: 340
+ CH3 C
O
O NH CH
NH
FormanidineC3H6N2O2
Mol. Wt.: 102.1
AcOH
N NO
H3C
C19H21N5O2Mol. Wt.: 351
Stage-5
+ 2 NH3 +CH3COOH
AmmoniaH6N2
Mol. Wt.: 34.1C2H4O2
Mol. Wt.: 60
Acetic acid
NH
NN
O
Stage-6:
Stage-5 compound undergoes condensation with 2-Bromo butane in presence of dimethyl sulfoxide medium gives stage-6 compound.
+ CH2 CH
Br
CH3CH3
C4H9BrMol. Wt.: 137
2-Bromo butane
+ K2CO3
Potassiumcarbonate
Mol. Wt.: 138
DMSOKOH
C23H29N5O2Mol. Wt.: 407.5
Stage-6
+KHCO3+KBr
Mol. Wt.: 100
Potassiumbicarbonate
Mol. Wt.: 119
Potassiumbromide
N NO
H3C
C19H21N5O2Mol. Wt.: 351
Stage-5
NH
NN
O
N NO
H3CN
NN
OCH
H3C
CH2
H3C
Stage-7:
Stage-6 on doing hydrolysis with aqueous hydrogen bromide under refluxing water forms stage-7 compound which is an intermediate (A)
C23H29N5O2Mol. Wt.: 407.5
Stage-6
+ aq. HBr
Hydrogenbromide
Mol.Wt.:81
stage-7C22H27N5O2
Mol. Wt.: 393.5
+CH3Br
Methyl bromideCH3Br
Mol. Wt.: 95
WaterN NO
H3CN
NN
OCH
H3C
CH2
CH3
N NHO
N
NN
OCH
H3C
CH2
CH3
Stage-8:
Benzoic acid-2-bromo-2-(3,5-dichloro phenyl)-[1,3]dioxolan-4-yl ester on treatment with 1,2,4-triazole with potassium carbonate and water in the presence of sodium hydroxide forms stage-8 compound.
Cl
ClO
O
O C
OBr
Benzoic acid 2-bromo-2-(3,5-dichloro-phenyl)-[1,3]dioxolan-4-yl ester
NH
NN
1,2,4-triazole
+
C2H3N3Mol. Wt.: 69.1
C16H11BrCl2O4Mol. Wt.: 418.1
+ K2CO3
Potassiumcarbonate
Mol. Wt.: 138 Cl
ClO
O
OH
NN
N
C11H9Cl2N3O3Mol. Wt.: 302
Stage-8
+ KBr +KHCO3
Potassiumbromide
Mol. Wt.: 119
Potassiumbicarbonate
Mol. Wt.: 100
+ H2O
water
Mol.Wt.:18
C
O
OH +
C7H6O2Mol. Wt.: 122
Benzoic acid
NaOH
Stage-9:
Stage-8 compound on condensation with Methane sulphonyl chloride forms the stage-9 compound which is an intermediate (B).
Cl
ClO
O
OH
NN
N
C11H9Cl2N3O3Mol. Wt.: 302
Stage-8
CH3 S
O
O
Cl
CH3ClO2SMol. Wt.: 114.6
Methanesulfonyl chloride
+
Cl
ClO
O
ON
N
N
SO
OCH3
C12H11Cl2N3O5SMol. Wt.: 380
Stage-9
HCl
Hydrochloricacid
+
Mol.Wt.:36.5
Tri ethyl amine
Stage-10:
Intermediate (A) on condensation with intermediate (B) with KOH in the presence of DMF as a solvent medium forms the Itraconozole crude and the product is finally purified with solvent.
N NOH N
NN
OCH
CH3 CH2
CH3stage-7C22H27N5O2
Mol. Wt.: 393.5
Cl
ClO
O
O
NN
NS
O
O
CH3
+
C12H11Cl2N3O5SMol. Wt.: 380
Stage-9
Cl
ClO
O
O
NN
N
S
O
O
CH3OH
N N N
NN
OCH
CH3 CH2
CH3
C33H34Cl2N8O4Mol. Wt.: 677.6
Itraconozole
+
CH4O3SMol. Wt.: 96
Methanesulfonic acid
Methanol
FLOW CHART OF ITRACONOZOLE
Methoxy phenyl piperazine HClp-Nitro chloro Benzene
Di-methyl sulphoxideReactor
Centrifuge
DMSO to recoveryHCl gas to scrubbing
Stage-1
Stage-1
Stage-1 productNickle catalyst
PalladiumMethanol
Reactor
Centrifuge Water to waste
Stage-2
Stage-2
Spent nickle catalystFiletaration
Methanol to recovery
Stage-2 productPhenyl chloro acetate
TolueneReactor
Centrifuge
Toluene to recoveryHCl gas to scrubbing
Stage-3
Stage-3
Stage-3 productHydrazine hydrate
1,4-DioxaneReactor
Stage-4
Stage-4
Spent dioxane
Centrifuge Phenol
Stage-4 productFormanidine
Acetic acidReactor
Centrifuge
Stage-5
Stage-5
Spent Acetic acidRelease of ammonia
Acetic acid
Stage-5 product2-bromo butane
DMSOPotassium carbonatePotassium hydroxide
Reactor
Centrifuge
Stage-6
Stage-6
Filetaration
Spent DMSO
Potassium bicarbonate& potassiunm bromide
Stage-6 productAqueous hydrogen bromide
WaterReactor
Centrifuge
Stage-7
Stage-7
Methyl bromide
Waste water to recovery
Reactor
Centrifuge
Stage-8
Stage-8
Filetaration
Benzoic acid-2-bromo-2-(3,5-dichloro phenyl)-[1,3]dioxolan-4-yl ester
1,2,4-triazolePotassium carbonate
WaterSodium hydroxide
Forms Potassium bicarbonatePotassium bromide &Benzoic acid
Stage-8 productMethane sulphonyl chloride
Tri ethyl amineReactor
Centrifuge
Stage-9
Stage-9
Spent Tri ethyl amine to recoveryHCl gas to scrubbing
Stage-7 productStage-9 product
MethanolReactor
Centrifuge
Stage-10
Stage-10
Methanol to recovery
Methane sulfonic acid
LANSOPRAZOLE
The product can be manufactured in five stages
Stage-1:
The condensation of 2, 3-dimethyl-4-nitropyridine with 2, 2, 2-trifluoroethanol by means of Potassium carbonate in presence of hot HMPT to form 2, 3-dimethyl-4-(2, 2, 2-trifluoroethoxy) pyridine N-oxide
NO
H3C
CH3
N+
O–
O
C7H8N2O3Mol. Wt.: 168.2
2,3-dimethyl-4-nitropyridineN-oxide
+
2,2,2-trifluoroethanol
FF
FOH
C2H3F3OMol. Wt.: 100
K2CO3HMPT
NO
H3C
CH3
O CF3
C9H10F3NO2Mol. Wt.: 221.2
KNO2+
+
Potassiumcarbonate
CK2O3Mol. Wt.: 138
Potassium nitriteKNO2
Mol. Wt.: 85
+KOH
Potassiumhydroxide
Mol. Wt.: 56
+CO2
Carbondioxide
Mol. Wt.: 44
Stage-1
Stage-2:
Stage-1 compound undergoes isomerisation in presence of acetic anhydride to form the 2 - (hydroxyl methyl)-3-methyl-4-(2, 2, 2-trifluoroethoxy) pyridine
NO
H3C
CH3
O CF3
Stage-1
(CH3CO)2ON
CH2
CH3
O CF3HO
C9H10F3NO2Mol. Wt.: 221.2
C9H10F3NO2Mol. Wt.: 221.2
Stage-2
Stage-3:
Stage-2 compound undergoes reaction with thionyl chloride in presence of Chloroform to form the corresponding chloromethyl derivative.
N
CH2
CH3
O CF3HO
C9H10F3NO2Mol. Wt.: 221.2
Stage-2
+ SOCl2
Thionylchloride
Mol. Wt.: 119
CHCl3
N
CH2
CH3
O CF3Cl
C9H9ClF3NOMol. Wt.: 239.6
Srage-3
+SO2
Sulfurdioxide
Mol. Wt.: 64.1
+ HCl
Hydrochloricacid
Mol. Wt.: 36.5
Stage-4:
Stage-3 compound undergoes condensation with 2-mercaptobenzimidazole by means of sodium methoxide in presence of methanol solvent medium to form 2 - (2-benzimidazolylthiomethyl) -3-methyl-4-(2,2,2-trifluoroethoxy) pyridine
N
CH2 CH3
O CF3Cl
C9H9ClF3NOMol. Wt.: 239.6
Srage-3 2-mercaptobenzimidazole
N
HN
SH
C7H6N2SMol. Wt.: 150
+
N
CH2 CH3
O CF3S
N
HN
C16H14F3N3OSMol. Wt.: 353.4
Stage-4
+HCl
Hydrochloricacid
Mol. Wt.: 36.5
MethanolNaOMe
.
Stage-5:
Finally, Stage-4 compound is oxidised with m-Chloro per benzoic acid in presence of chloroform to form the stage-4 compound.
N
CH2
CH3
O CF3S
N
HN
C16H14F3N3OSMol. Wt.: 353.4
Lansoprazole
+CHCl3
N
CH2
CH3
O CF3S
N
HN
(O)
oxygenMol. Wt.: 16
m-CPBA
O
C16H14F3N3O2SMol. Wt.: 369.4
Stage-4
FLOW CHART OF LANSOPRAZOLE
2, 3-dimethyl-4-nitropyridine2, 2, 2-trifluoroethanol
Potassium carbonateHMPT
Reactor
Centrifuge
CO2 gas to scrubbing
KOH & KNO2 for use
Stage-1:
Stage-1
Stage-1Acetic anhydride Reactor
Stage-2:
Finished product
Stage-2Thionyl chloride
Chloroform
Stage-3:
Reactor
Centrifuge SO2 to scrubbing& HCl to reuse
Stage-3 product
Stage-32-mercaptobenzimidazole
Sodium methoxideMethanol
Stage-4:
Reactor
Centrifuge
Methanol to recovery
HCl to use
Stage-4 product
LORNOXICAM
The product is manufactured in six stages.
Stage-1:
2, 5-dichlorothiophene and Chlorosulfonic acid undergoes condensation produces stage-1 compound.
Chloroform is the solvent used in the process.
2,5-dichlorothiophene
S
Cl
Cl
C4H2Cl2SMol. Wt.: 153
+
Cl
SO O
OH
Chloro sulfonic acidClHO3S
Mol. Wt.: 116.5
Chloroform
S
Cl
Cl
SO O
Cl
C4HCl3O2S2Mol. Wt.: 251.5
Stage-1
+ H2O
Water
Mol. Wt.: 18
Stage-2:
Stage-1 compound reacts with Mono methyl amine in presence of chloroform solvent medium forms the
stage-2 compound.
S
Cl
Cl
SO O
Cl
C4HCl3O2S2Mol. Wt.: 251.5
Stage-1
+Chloroform
Mono methyl amine
H2N CH3
CH5NMol. Wt.: 31.1
S
Cl
Cl
SO O
NH CH3
C5H5Cl2NO2S2Mol. Wt.: 246
Stage-2
+ HCl
Hydrochloric acid
Mol. Wt.: 36.5
Stage-3:
Stage-2 compound reacts with Carbon dioxide and hydrogen in presence of Butyl lithium forms the Stage-3 compound. Methanol is the solvent used in this process.
SCl
Cl
SO O
HN CH3
C5H5Cl2NO2S2Mol. Wt.: 246
Stage-2
++ CO2
Carbon Dioxide
Mol. Wt.: 44
+ 2 H
Hydrogen
Mol. Wt.: 2
S
S NH
O OCH3
O
OH
ClBuLiMeOH
HCl
Hydrochloric acid
Mol. Wt.: 36.5C6H6ClNO4S2Mol. Wt.: 255.7
Stage-3
Stage-4:
Stage-3 compound undergoes reaction with methanol in presence of Phosphorous pentachloride and methanol solvent medium forms the stage-4 compound.
S
S NH
O OCH3
O
OH
Cl
C6H6ClNO4S2Mol. Wt.: 255.7
Stage-3
PCl5MeOH S
S NH
O OCH3
O
O
Cl
CH3
C7H8ClNO4S2Mol. Wt.: 269.7
+
MethanolCH4O
Mol. Wt.: 32
Stage-4
+ H2O
Water
Mol.Wt.: 18
Methanol
Stage-5:
Stage-4 compound reacts with Methyl iodo acetate in presence of a strong base; sodium hydride undergoes the following reaction and forms the stage-5 compound.
S
S NH
O OCH3
O
O
Cl
CH3
C7H8ClNO4S2Mol. Wt.: 269.7
Stage-4C3H5IO2
Mol. Wt.: 200
+NaH
S
S N
O O
CH3O
O
Cl
CH3
C10H12ClNO6S2Mol. Wt.: 341.8
Stage-5
+ HI
Hydrogen Iodide
Mol. Wt.: 127.9
OCH3
OIO
CH3O
Methyl iodo acetate
Stage-6:
Stage-5 product undergoes cyclization in presence of sodium methoxide forms the stage-6 compound.
The reacdtion proceeds as per the below equation.
S
S N
O O
CH3O
O
Cl
CH3
C10H12ClNO6S2Mol. Wt.: 341.8
Stage-5
OCH3
OS
SN
O OCH3
HO
Cl
C9H8ClNO5S2Mol. Wt.: 309.7
Stage-6
NaOMe H2O+
Water
Mol. Wt.: 18
H2O
Water
Mol. Wt.: 18
+ + CH3OH
MethanolMol.Wt.: 32
O
OCH3
Stage-7:
Stage-6 compound undergoes reaction with Pyridine-2-ylamine forms the final compound Lornoxicam
which undergoes as per the below equation. Methanol is the solvent used in this process.
N
H2N
C5H6N2Mol. Wt.: 94
Pyridin-2-ylamine
+
N
HN
S
SN
O OCH3
HO
Cl
C9H8ClNO5S2Mol. Wt.: 309.7
Stage-6
O
OCH3
S
SN
O OCH3
HO
Cl
O
CH3OH
Methanol
Mol. Wt.: 32C13H10ClN3O4S2Mol. Wt.: 371.8
Lornoxicam
+Methanol
FLOW CHART OF LORNOXICAM
2, 5-dichlorothiopheneChlorosulfonic acid
ChloroformReactor
Water Waste water ro recoveryCentrifuge
Stage-1
Stage-1
Reactor
Centrifuge
Stage-2
Stage-2
Stage-1Mono methyl amine
Chloroform
Waste HCl to recovery
Reactor
Centrifuge
Stage-3
Stage-3
Stage-2Carbon Dioxide
HydrogenButyl lithium
Methanol
Spent solvent to recovery
Waste HCl to recovery
Reactor
Centrifuge
Stage-4
Stage-4
Stage-3Methanol
PCl5
Spent solvent to recovery
Water Waste water to recovery
Reactor
Centrifuge
Stage-5
Stage-5
Stage-4Methyl iodo acetate
Sodium Hydride
Hydrogen Iodide
Reactor
Centrifuge
Stage-6
Stage-6
Stage-5Sodium methoxide
Water
Waste water & Methanol to recovery
Reactor
Centrifuge
Stage-7
Stage-6Pyridine-2-ylamine
MethanolMethanol to recovery
Final product
MONTELUKAST SODIUM
Montelukast Sodium is produced in 6 stages.
Stage-:1:
On condensation of 7-Chloro-2-methyl quinoline with Benzene-1, 3-dicarbaldehyde by means of acetic anhydride in presence of acetic acid solvent medium to form the stage-1 product.
C8H6O2Mol.Wt.: 134
+ +
C10H8ClNMol. Wt.: 177.6
O
H
Benzene 1,3-dicarbaldehyde
C18H12ClNOMol. Wt.: 293.7
3-[2-(7-Chloro-quinolin-3-yl)-vinyl]-benzaldehyde
H2O
Mol. Wt.: 18
Water
HONCl CH3
7-Chloro-2-methylquinoline
NCl
O H
Ac2O
AcOH
Stage-2:
Stage-1 compound on reacting with Vinyl Magnesium Bromide and water by means of sodium chloride and ammonium acetate is used as a catalyst in presence of toluene solvent medium to form the stage-2 product.
C18H12ClNOMol. Wt.: 293.7
NCl
O H
+Mg CH2
Br
Vinylmagnesiumbromide Water
+
C2H3BrMgMol. Wt.: 131
NaCl
NCl
OH
C20H16ClNOMol. Wt.: 321.1
Stage-1
Stage-2
MgBrOH
hydroxy magnesium bromideBrHMgO
Mol. Wt.: 121
H2O+
H2OMol. Wt.: 18
CH3COONH4
Toluene
Stage-3:
Stage-2 compound on condensation with 1-(2-Iodophenyl) ethanone in presence of Palladium acetate and water in presence of acetonitrile solvent medium to obtain the stage-3 product
NCl
OH
C20H16ClNOMol. Wt.: 321.1
Stage-2
+O
I
1-(2-iodo phenyl ) ethanoneC8H7IO
Mol. Wt.: 246
Pd(OCOCH3)
CH3CN
NCl
OH
O
C28H24ClNO2Mol. Wt.: 441.9
Stage-3Hydrogen Iodide
H I +
Mol. Wt.:127.9
Stage-4:
Stage-3 reacts with Methyl magnesium bromide and water by means of CeCl3 in Acetonitrile solvent medium to attain the stage-4 product.
NCl
OH
O
C28H24ClNO2Mol. Wt.: 442
Stage-3Methyl magnesium
bromide
Hydroxy Magnesiumbromide
+
Water
Acetonitrile
CeCl3CH3BrMg+
CH3BrMgMol. Wt.: 119
H2O+
Mol. Wt.: 18
NCl
OH
OH
C29H28ClNO2Mol. Wt.: 458
Stage-4
MgBrOH
Mol. Wt.: 121
Stage-5:
Stage-4 reacts with Methane sulfonyl chloride in the presence of n, n- Di isopropyl ethylamine and toluene solvent medium to form the stage-5 compound.
NCl
OH
OH
C29H28ClNO2Mol. Wt.: 458
Stage-4
+
CH3
SO O
Cl N,N,Diisopropylethylamine
+ HCl
Hydrochloric acid
Toluene
Methanesulfonyl chlorideCH3ClO2S
Mol. Wt.: 114.6
NCl
OH
CH3
S OO
O
C30H30ClNO4SMol. Wt.: 536.1
Stage-5
Mol. Wt.: 36.5
Stage-6:
Stage-5 product on reaction with (1-Mercapto methyl cyclopropyl) acetic acid with butyl lithium in presence of tetra hydro furan solvent medium to form the final compound
NCl
OH
CH3
S OO
O
C30H30ClNO4SMol. Wt.: 536.1
Stage-5
+
Methanesulfonic acid
O
OHSH
C6H10O2SMol. Wt.: 146
(1-Mercaptomethyl-cyclopropyl)acetic acid
NCl
OH
CH3
S OO
OH
Stage-5
S
O
O
+
CH4O3SMol. Wt.: 96
+ NaOH
Sodiumhydroxide
Mol. Wt.: 40
n-BuLi
THFNa
+H2O
Water
Mol. Wt.: 18C35H35ClNNaO3S
Mol. Wt.: 608.2
FLOW CHART
7-chloro-2-methyl quinolineBenzene-1,3-dicarbaldehyde
Acetic anhydrideAcetic acid
Stage-1
Reactor
Reactor
Centrifuge
Stage-1
Acetic acid to recovery
Waste water
Stage-2
Stage-1Vinylmagnesiumbromide
AmmoniumacetateWater
TolueneSodium chloride
Reactor
Hydroxy magnesiumbromide to disposal
Toluene to recovery
Centrifuge
Filteration Sodium chloride solution
Reactor
Stage-2
Stage-3
Stage-22-Iodophenyl ethanone
Palladium acetateAcetonitrile
Palladium acetate solution to waste
Reactor
Centrifuge
Stage-3
Acetonitrile to recovery
Water
Stage-4
Stage-3Methylmagnesiumbromide
AcetonitrileCeriumchloride
Water
Acetonitrile to recoveryReactor
Centrifuge
Stage-4
Cerium chloride solution to waste
Filteration Hydroxy magnesium bromide to disposal
Stage-5
Stage-4Methyl sulfonyl Chloride
n,n-Di isopropyl EthylamineToluene
Reactor
Centrifuge
Stage-5
Toluene to recovery
Waste HCl
Stage-6
Stage-5Mercapto methylcyclopropane acetic acid
Sodium Hydroxiden-Butyl lithium
Tetra hydro furan
Reactor
Centrifuge
Pharma
THF to recovery
Waste water
OMEPRAZOLE
The product is produced in five stages.
Stage-1:
3, 5-Lutidine undergoes oxidation with Hydrogen peroxide initially in Acetic acid. Then the reaction mass
will be subjected to Nitration with Nitric acid and Sulfuric acid mixture.
3,5-Lutidine
+ H2O2 + HNO3
Hydrogen Peroxide
Mol. Wt.:34Nitric acid
Mol. Wt.: 63
N+O-
CH3CH3
N+O
O-
Stage-1C7H8N2O3
Mol. Wt.: 168.
+ 2 H2O
Water
Mol. Wt.:36
N
H3C CH3
C7H9NMol. Wt.: 107
H2O, H2SO4Acetic acid
Stage-2:
Stage-1 compound on reaction with Sodium methoxide, Sodium Hydroxide and Dimethyl sulfate in presence
of methanol solvent medium by means of water produces stage-2 compound. The reaction proceeds as
per the below equation.
NO
CH3CH3
NO
OStage-1
C7H8N2O3Mol. Wt.: 168.2
+
Sod.methoxideMol. Wt.:54
+ 2 NaOH
Sodium hydroxideMol. Wt.: 80
MeOH
+NaNO2+H2O
Sodium NitriteWater
NO
CH3CH3
COOH
Stage-2C8H9NO3
Mol. Wt.: 167.2
CH3ONa + (CH3)2SO4
Di methyl sulfoxideMol. Wt.:126
Water
+Na2SO4
Sod.Sulphate
+CH3OH
MethanolNNaO2
Mol. Wt.: 69H2O
Mol. Wt.: 18Na2O4S
Mol. Wt.: 142CH4O
Mol. Wt.: 32
Stage-3:
Stage-2 product on reaction with Thionyl chloride & sodium hydroxide produces stage-3 compound in
presence of toluene solvent medium.
NO
CH3CH3
COOH
Stage-2C8H9NO3
Mol. Wt.: 167.2
+ SOCl2
Thionyl Chloride
Toluene
NO
CH3CH3
COCl
Stage-3
+SO2+NaCl
Sulphur dioxideSodium Chloride
+ H2O
Water
+ NaOH
Sodium HydroxideCl2OS
Mol. Wt.: 119HNaO
Mol. Wt.: 40
O2SMol. Wt.: 64.1
H2OMol. Wt.: 18
ClNaMol. Wt.: 58
C8H8ClNO2Mol. Wt.: 185.6
Stage-4:
Stage-3 product on condensation with 5-Methoxy -2-Mercapto benzimidazole in presence of C.S. Lye
Produces stage-4.Toluene is the solvent medium
NO
CH3CH3
COCl
Stage-3
N
NH
OCH3
HS
2-Mercapto-5-methoxy benzimidazoleC8H8N2OS
Mol. Wt.: 180
+Toluene
SN
NH
N
CH3
O CH3CH3
O+
Stage-4
C16H17N3O3SMol. Wt.: 331
Mol. Wt.:36.5
C.S.Lye
HCl
O
Hydrochloricacid
O
C8H8ClNO2Mol. Wt.: 185.6
Stage-5: Omeprazole
Above stage-4 compound on reaction with Hydrogen Peroxide produces stage-5 pharma. Methanol and
Acetone are used in the process.
SN
NHN
CH3
O CH3CH3
O
+
Stage-4C16H17N3O3SMol. Wt.: 331
Oomeprazole
C17H19N3O3SMol. Wt.: 345.
+ H2O2
HydrogenPeroxide
Mol. Wt.: 34
MeOHAcetone S
NO
CH3
NHN
CH3
O CH3CH3
H2O
WaterMol. Wt.: 18
O O
FLOW CHART OF OMEPRAZOLE
Stage-1 3,5-LutidineHydrogen Peroxide
Nitric acidSulphuric acid
Acetic acidWater
Reactor
Stage-1
Waste waterCentrifuge
Stage-2Stage-1
MethanolSod.Methoxide
DimethylsulphateSodium Hydroxide
Water
Reactor
Stage-2
Inorganic solid waste solutionCentrifuge
Stage-3
Methanol to recovery
Stage-2Thionylchloride
AmmoniumpersulphateToluene
Water
Reactor
Stage-3
Waste waterCentrifuge
SulphurdioxideHCl to scrubber
Layerseperator Toluene to recovery
Stage-4Stage-3
5-Methoxy mercaptobenzimidazole
C.S.LyeToluene
Reactor
Layerseperator
CentrifugeWater Waste water
Stage-4
Stage-5Stage-5
MethanolAcetone
Hydrogen peroxide
Reactor
Centrifuge Acetone to recovery
Pharma
IPA to recovery
Toluene to recovery
ONDANSETRON
The compound can be prepared in five stages.
Stage-1:
Condensation of 2-bromo aniline with cyclohexane-1,3-dione gives bromo enaminone in presence of
methanol solvent medium.
2-Bromo Aniline Cyclohexane-1,3-dione
+ + H2O
Water
Mol. Wt.: 18
O
ONH2
Br
C6H6BrNMol. Wt.: 172
C6H8O2Mol. Wt.: 112
Methanol
NH
BrO
C12H12BrNOMol. Wt.: 266
Stage-1
Stage-2:
Staeg-1 compound is N-methylated with Iodo methane by means of NaH in presence of benzene medium
affording tertiary enaminone.
NH
BrO
C12H12BrNOMol. Wt.: 266
Stage-1
+
Methyl Iodide
H3C I
CH3IMol. Wt.: 141.9
NaH
N
BrO
CH3
C13H14BrNOMol. Wt.: 280.2
Stage-2
+ HI
HIMol. Wt.: 127.9
Hydrogen Iodide
C6H6
Stage-3:
Stage-2 compound is treated with dimethyl amio methylene iodide (Eschenmoser salt) by means of lithium
di isopropyl amide in presence of THF solvent medium affords dimethyl amino methyl derivative.
N
BrO
CH3
C13H14BrNOMol. Wt.: 280.2
Stage-2
N
H3C
H3C
CH2
I
+
C3H8INMol. Wt.: 185
Dimethyl amiomethylene iodide
LDATHF N
BrO
CH3
N
CH3
CH3
C16H21BrN2OMol. Wt.: 337.3
Stage-3
+ HI
Hydrogen iodideHI
Mol. Wt.: 127.9
Stage-4:
Stage-3 compound is then coupled with 2-methyl indole in presence of DMF solvent medium to form the
stage-4 compound.
N
BrO
CH3
N
CH3
CH3
C16H21BrN2OMol. Wt.: 337.3
Stage-3
+NHN
CH3
C4H6N2Mol. Wt.: 82
2-methyl indole
N
BrO
CH3
N N
CH3
DMF
N, N-dimethyl amine
HN
CH3H3C+
C2H7NMol. Wt.: 45.1
C18H20BrN3OMol. Wt.: 374.3
Stage-4
Stage-5:
Stage-4 compound undergoes cyclization by means of palladium acetate and triethyl amine in presence of
acetonitrile forms the final compound.
N
BrO
CH3
N N
CH3
C18H20BrN3OMol. Wt.: 374.3
Stage-4
+Pd(OAc)2
Et3NN
O
CH3
N N
CH3
C18H19N3OMol. Wt.: 293.4
Ondansetron
HBr
Hydrobromicacid
Mol. Wt.: 80.9
CH3CN
FLOW CHART OF ONDANSETRN
2-bromo anilinecyclohexane-1,3-dione
MethanolReactor
Centrifuge
Spent methanol to recovery
Waste water
Stage-1
Stage-1
Stage-1Iodo methane
Sodium hydrideBenzene
Reactor
Centrifuge
Spent MLs to recovery&HI gas to scrubbing
Stage-2
Stage-2
Stage-2dimethyl amio methylene iodide
lithium di isopropyl amideTHF
Reactor
Centrifuge
THF to recovery &HI gas to scrubbing
Stage-3
Stage-3
Reactor
Centrifuge
Stage-32-methyl indole
DMFSpent DMF to recovery
N,N-dimethyl amine
Stage-4
Stage-4
Reactor
Centrifuge
Stage-4palladium acetate
triethyl amineacetonitrile
Stage-5
Acetonitrile to recovery &HBr gas to scrubbing
Final compound
OXYCLOZANIDE
The compound can be prepared in five stages.
Stage‐1:
2, 4‐Dichlorophenol is treated with Nitric acid in presence of water to produce stage‐1 compound.
OH
Cl
Cl
C6H4Cl2OMol. Wt.: 163
2,4-Dichloro-phenol
+ HNO3
Nitric acid
Water
OH
Cl
Cl
C6H3Cl2NO3Mol. Wt.: 208
2,4-Dichloro-Nitrophenol
+NO2
H2O
Water
Mol. Wt.: 18Mol. Wt.: 63
Stage‐2:
STEP‐A
Sodium hydroxide, Sulfur and water react together in presence of water medium to form the sodium sulfide. The reaction proceeds as per the below equation.
Water
SodiumHydroxide
2 NaOH
Mol.Wt.:80
+ + + + +H2O
WaterMol.Wt.:18
3 S
Mol.Wt.:96
Na2S2
SodiumSulphide
Mol.Wt.:110
H2
Hydrgen
SO2
Sulphurdioxide
Mol.Wt.:2 Mol.Wt.:64
H2O
WaterMol.Wt.:18
STEP‐B
Sodium sulfide reacts with 2,4‐Dichloro nitro phenol and water in presence of mono chloro benzene forms the stage‐2 compound.
OH
Cl
Cl
C6H3Cl2NO3Mol. Wt.: 208
2,4-Dichloro Nitrophenol
+
O2NNa2S2
Sodium sulphide
+ H2O
Water
Mol. Wt.: 18
WaterMCB
OH
Cl
ClNH2
Stasge-2C6H5Cl2NO
Mol. Wt.: 178
+ Na2S2O3
Sodiumdithionate
Mol. Wt.: 158Na2S2
Mol. Wt.: 110
Stage‐3:
3,5,6‐Trichloro Salicylic acid is treated with Thionyl chloride in presence of Mono chloro benzene to produce stage‐3product.
Thionyl chloride3,5,6-trichlorosalicylic acid
+
Sulphur dioxide
SO2+ + HCl
Hydrochloricacid
Mol.Wt.:36.5
HO
O
HO
Cl Cl
Cl
C7H3Cl3O3Mol. Wt.: 241.5
S
O
Cl
Cl
Cl2OSMol. Wt.: 119
MCB
HO
O
Cl
Cl Cl
Cl
C7H2Cl4O2Mol. Wt.: 259.9
Stage-3O2S
Mol. Wt.: 64.1
Stage‐4:
Stage‐2 & stage‐3 products react together in presence of mono chloro benzene to form stage‐4.
Stasge-2C6H5Cl2NO
Mol. Wt.: 178
+
Stage-3C7H2Cl4O2
Mol. Wt.: 259.9
MCB
Stage-4
HCl
Hydrochloricacid
Mol. Wt.: 36.5
OH
Cl
Cl
Cl
Cl
O
OH
Cl
Cl
H2N
OH
Cl
Cl
Cl
O
OH
Cl
Cl
NH
C13H6Cl5NO3Mol. Wt.: 401.5
+
Staeg‐5:
Stage‐4 product on purification with Carbon in presence of Acetone produces Oxyclozanide.
Stage-4
OH
Cl
Cl
Cl
O
OH
Cl
Cl
NH
C13H6Cl5NO3Mol. Wt.: 401.5
AcetoneCarbon
OH
Cl
Cl
Cl
O
OH
Cl
Cl
NH
C13H6Cl5NO3Mol. Wt.: 401.5
Oxyclozanide
FLOW CHART OF OXYCLOZANIDE
2, 4-DichlorophenolNitric acid
WaterReactor
Centrifuge Water to waste
Stage-1
Stage-1
Sodium hydroxideSulfurWater
Reactor Hydrogen & sulfur gasses to scrubbing
Centrifuge Inorganic salt solution to waste
Reactor
2,4-Dichloro nitro phenolSodium sulfide
WaterMono chloro benzene
Spent MLs
Centrifuge Inorganic salt solution to waste
Stage-2
Stage-2
3,5,6-Trichloro Salicylic acidThionyl chloride
Mono chloro benzeneReactor
Centrifuge
Spent MLs &SO2 & HCl gasses to scrubbing
Stage-3
Stage-3
Stage-2Stage-3
Mono chloro benzeneRaector
Centrifuge
Spent MLsHCl gas to scrubbing
Stage-4
Stage-4
Stage-2Stage-3
Mono chloro benzeneRaector
Centrifuge
Acetone to recovery
Spent carbon
Final product
Stage-5
RITONAVIR
The product can be prepared in five stages
Stage-1:
(2S, 3S, 5S)-2-amino-3-hydroxy-5-(tert-butyl oxy carbonyl) amino-1,6-diphenylhexane hemi succinic acid salt and Carbnic acid.4-nitrophenyl-5-thiazolyl methyl ester condense to produce stage-1 compound. Sodium bicarbonate and Sodium hydroxide are used in the condensation.
NH2
NH
O O
CH3 CH3
CH3
OHCOOH
CH2CH2
COOH
SN
O
O
O
NO2
NHNH
O O
CH3 CH3
CH3
OHO
O
SN
+ + NaOH
Sodiumhydroxide
Sodimbicarbonate
Carbnic acid.4-nitrophenyl-5-thiazolylmethyl ester
(2S,3S,5S)-2-amino-3-hydroxy-5-(tert-butyloxycarbonyl) amino-1,6-diphenyl
hexane hemi succinic acid salt
+CH3COONa + H2O2
Water
Mol. wt.:34
Stage-1Sodium acetate
+
NaHCO3+
p-nitro phenol
H2O
NO2
OH
C27H38N2O7Mol. Wt.: 502.6
C11H8N2O5SMol. Wt.: 280.3
CHNaO3Mol. Wt.: 84
HNaOMol. Wt.: 40
C28H35N3O5SMol. Wt.: 525.7
C6H5NO3Mol. Wt.: 139
C4H6Na2O4Mol. Wt.: 164
+CO2
CO2Mol. Wt.: 44
Carbon Dioxide
Stage-2:
Stag-1 is subjected to cyclization with water and hydrochloride in presence of n-Hexane and 1, 4-Dioxane to form the stage-2 compound.
NHNH
O O
CH3 CH3
CH3
OHO
O
SN Stage-1
C28H35N3O5SMol. Wt.: 525.7
NH NH2 .HClOHO
O
SN
1,4-Dioxane
Stage-2
+
CH3 CH3
CH3
+ H2O
Water
Mol. Wt.: 18
+ HCl
Mol. Wt.: 36.5
Hydrochloric acid
n-Hexane
OHO
O
C5H10O3Mol. Wt.: 118
C23H28ClN3O3SMol. Wt.: 462
Stage-3:
Step-A: Stage-2 compound undergoes base hydrolysis to form the free base compound.
NH NH2 .HClOHO
O
SN Stage-2
C23H28ClN3O3SMol. Wt.: 462
++
NaOHNaCl + H2O
WaterSodiumchloride
Sodiumhydroxide
Free base
Mol. wt.:40 Mol. wt.:58.5 Mol. wt.:18
H2O
NHNH2
OHO
O
SN
C23H27N3O3SMol. Wt.: 425.5
Step-B:
LiO
O
CH3
NH
CH3O
NCH3
SN
CH3CH3
+ HCl + LiCl
N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl
amino)carbonyl)-L-valine.Lithium salt
Mol. wt.:319C14H22LiN3O3S
Mol. wt.:313.00C14H23N3O3S
OH
O
CH3
NH
CH3O
NCH3
SN
CH3CH3
Mol. wt.:42
Lithium chlorideFree acidHydrochloricacid
Mol.Wt.:36.5
Step-C:
OH
O
CH3
NH
CH3O
NCH3
SN
CH3CH3
O
O
CH3
NH
CH3
O
N
CH3S
NCH3
CH3
OO
CH3
CH3
HCl
+
Cl
O
OCH2 CH
CH3
CH3+
Mol. wt.:397C19H31N3O4S
Mol. wt.:36.5Hydrochloric acid
Mol. wt.:313C14H23N3O3S
Free acid Isobutylchloroformate
Mol. wt.:136.5C5H9O2Cl
Stage-4:
NS
CH3CH3
N
O
NH
CH3CH3
NH
O OHNH
O
O
N
SCH3
Ritonavir crudeC37H48N6O5S2Mol. wt.:720.1
C37H48N6O5S2Mol. wt.:720.1
Ritonavir form-II
NS
CH3CH3
N
O
NH
CH3CH3
NH
O OHNH
O
O
N
SCH3
Ethyl acetaten-heptane
RIT-form-II(seedling)
Step-5:
NS
CH3CH3
N
O
NH
CH3 CH3
NH
O OHNH
O
O
N
SCH3
NS
CH3CH3
N
O
NH
CH3CH3
NH
O OHNH
O
O
N
SCH3
C37H48N6O5S2Mol. wt.:720.1
C37H48N6O5S2Mol. wt.:720.1
Ethyl acetaten-heptane
RIT-form-I(seedling)
Ritonavir form-II Ritonavir form-I
FLOW CHART OF RITONAVIR
Stage-1
Reactor Water to recovery
Centri fuge
Stage-1
Water to waste
(2S,3S,5S)-2-amino-3-hydroxy-5-(tert-butyloxycarbonyl) amino-1,6-diphenylhexane hemi succinic acid
Carbnic acid.4-nitrophenyl-5-thiazolyl methyl ester SodiumbicarbonateSodium hydroxide
Water
Reactor Toluene to recovery
Centri fuge
Stage-2
Water to waste
Layer saparate
Tolene to recovery
Satge-11,4-Di oxane
HCln-hexane
Water
Stage-2
Reactor Water to recovery
Centri fuge
Water to wasteLayer
saparate
salt solution
Stage-2Sodium hydroxide
HClIsobutyl chloro formate
Water
stage-3
Stage-3
Reactor n-heptene to recovery
Centri fuge
Stage-4
Water to wasteLayer
saparate
Ethyl acetate to recovery
Satge-3n-Heptane
Ethyl acetateWater
Stage-4
Stage-5
Reactor n-heptene to recovery
Centrifuge
Stage-5
Water to wasteLayer
saparate
Ethyl acetate to recovery
Satge-4n-Heptane
Ethyl acetateWater
ROSUVASTATIN CALCIUM
The product can be prepared in ten stages.
Stage-1:
The condensation of 4-fluoro benzaldehyde with 4-methyl-3-oxo pentanoic acid ethyl ester by means of
Piperidine and acetic acid in presence of benzene solvent medium gives the stage-1 compound.
CHO
F +
4-methyl-3-oxopentanoic acid ethyl ester
O
OO
C8H14O3Mol. Wt.: 158.2
C7H5FOMol. Wt.: 124
4-fluoro benzaldehyde
Piperidine/AcOHO
Benzene
F
O
O
C15H17FO3Mol. Wt.: 264.3
Stage-1
H2O
Mol. Wt.: 18Water
+
Stage-2:
Stage-1 is cyclized with S-methyl iso thio urea and oxidized with DDQ in presence of toluene solvent
medium affords the stage-2 compound. The reaction proceeds as per the below equation.
OF
O
O
C15H17FO3Mol. Wt.: 264.3
Stage-1
SCH3
NHH2N
C2H6N2SMol. Wt.: 90
S-methyl iso thio urea
+
OF O
N N
SCH3
C17H19FN2O2SMol. Wt.: 334
Stage-2
+
O
O
Cl
Cl
CN
CN
DDQC8Cl2N2O2
Mol. Wt.: 227
+Toluene
OH
OH
Cl
Cl
CN
CN
C8H2Cl2N2O2Mol. Wt.: 229
2,3-dichloro-5,6-dicyanohydroquinone
+H2O
WaterMol. Wt.: 18
Stage-3:
The oxidation of stage-2 compound with m-Chloro per benzoic acid with hydrogen peroxide in presence of
aqueous sodium hydroxide gives the stage-3 compound.
OF O
N N
SCH3
C17H19FN2O2SMol. Wt.: 334
Stage-2
m-CPBA/H2O2
Aq.NaOH
OF O
N N
SCH3O
O
C17H19FN2O4SMol. Wt.: 366
Stage-3
2 (O)+
OxygenMol. Wt.: 32
Stage-4:
Stage-3 compound is treated with methyl amine in presence of methane sulfonyl chloride gives the stage-
4 compound.
OF O
N N
SCH3O
O
C17H19FN2O4SMol. Wt.: 366
Stage-3
MeNH2
CH5NMol. Wt.: 31.1
+
Methhyl amine
Me SO2Cl
OF O
N N
SCH3
O
O
N CH3
C18H22FN3O4SMol. Wt.: 395.5
Stage-4
H2+
HydrogenMol. Wt.: 2
Stage-5:
The reduction of ester group of stage-4 compound with DIBAL H (Di-isobutyl aluminum hydride) in
presence of toluene solvent medium affords the resulting aldehyde.
OF
CH3
CH3O
N N
SCH3
O
O
N CH3
C18H22FN3O4SMol. Wt.: 395.5
Stage-4
DIBAL H
HF
CH3
CH3O
N N
SCH3
O
O
N CH3
H3C
H2C
OH
EthanolC2H6O
Mol. Wt.: 46.1
H2 +
C16H18FN3O3SMol. Wt.: 351
Stage-5
+
HydrogenMol.Wt.: 2
Stage-6:
Stage-5 compound is submitted to a Wittig condensation with the phosphorane in dry THF to give the
stage-6 product.
HF
CH3
CH3O
N N
SCH3
O
O
N CH3
C16H18FN3O3SMol. Wt.: 351
Stage-5
OO
TBDMSO
(Ph3)P
OCH3
C31H39O4PSiMol. Wt.: 534.7
+
Phosphorane compound
F
CH3
CH3
N N
SCH3
O
O
NCH3
OO
TBDMSO OCH3
C29H42FN3O6SSiMol. Wt.: 607.8
Stage-6
Dry THF Ph3P O+
Tri phenylphosphine oxide
C18H15OPMol. Wt.: 278.3
Stage-7:
The deprotection of stage-6 compound with HF in presence of THF solvent medium forms the Stage-7
compound.
F
CH3
CH3
N N
SCH3
O
O
NCH3
OO
TBDMSO OCH3
C29H42FN3O6SSiMol. Wt.: 607.8
Stage-6
HF
Hydrogen fluoride
Mol. Wt.: 20
+THF
F
CH3
CH3
N N
SCH3
O
O
NCH3
OO
HO OCH3
SiH3C CH3
F
C6H15FSiMol. Wt.: 134.3
Tert-butyl dimethyl silyl fluoride
C23H28FN3O6SMol. Wt.: 493.5
Stage-7
+
Stage-8:
The controlled reduction of stage-7 product with sodium boro hydride in diethyl methoxy borane affords
the stage-8 compound.
F
CH3
CH3
N N
SCH3
O
O
N CH3
OO
HO OCH3
C23H28FN3O6SMol. Wt.: 493.5
Stage-7
Et2BOMe/NaBH42 (H)
HydrogenMol. Wt.: 2
+
F
CH3
CH3
N N
SCH3
O
O
N CH3
OHO
HO OCH3
C23H30FN3O6SMol. Wt.: 495.6
Stage-8
Stage-9:
Stage-8 is hydrolyzed with NaOH in presence of ethanol solvent medium yielding the corresponding
sodium salt. The reaction showed as below.
F
CH3
CH3
N N
SCH3
O
O
NCH3
OHO
HO OCH3
C23H30FN3O6SMol. Wt.: 495.6
Stage-8
+ NaOH
SodiumhydroxideMol. Wt.: 40
Ethanol
F
CH3
CH3
N N
SCH3
O
O
N CH3
OHO
HO ONa
C22H27FN3NaO6SMol. Wt.: 503.5
Stage-9
H3C OH+
CH4OMol. Wt.: 32
Methanol
Stage-10:
Stage-9 compound is finally treated with calcium chloride in water yields the final compound. The reaction
proceeds as per the below equation.
F
CH3
CH3
N N
SCH3
O
O
N CH3
OHO
HO ONa
C44H54F2N6Na2O12S2Mol. Wt.: 1007
Stage-9
+ CaCl2
Calcium chlorideCaCl2
Mol. Wt.: 111
Water
F
CH3
CH3
N N
SCH3
O
O
N CH3
OHO
HO O
Ca2+
C44H54F2N6O12S2Ca2+
Mol. Wt.: 1001
Rosuvastatin calcium
2 NaCl+
2
2
Cl2Na2Mol. Wt.: 116.9
Sodium chloride
FLOW CHART OF ROSUVASTATIN CALCIUM
4-fluoro benzaldehyde4-methyl-3-oxo pentanoic acid ethyl ester
PiperidineAcetic acid
benzene
Reactor
Centrifuge
Solvent ml's to recovery
Waste water
Stage-1
Stage-1
Stage-1S-methyl iso thio urea
DDQToluene
Reactor
Centrifuge
Toluene to recovery
Waste water
Stage-2
Stage-2
Layerseparator 2,3-dichloro-5,6-dicyano
hydro quinone
stage-2Oxygen
m-CPBAHydrogen peroxideSodium hydroxide
Reactor
Stage-3
Stage-3
solvent ml's to recovery
Stage-3Methyl amine
Methane sulfonyl chlorideReactor
Centrifuge
Stage-4
Stage-4
solvent ml's to recovery
Hydrogen emission to scrubber
Stage-4Hydrogen DIBAL H
Reactor
Centrifuge
Stage-5
Stage-5
Ethanol
Stage-5Phosphorane compound
Dry THFReactor
Centrifuge
Stage-6
Stage-6
Solvent ml's to recovery
Triphenyl phosphine oxide
Stage-6Hydrogen fluorideTetra hydro furan
Reactor
Centrifuge
Stage-7
Stage-7
Solvent ml's to recovery
Tert-butyl dimethyl silyl fluoride
Stage-7Hydrogen
Diethyl methoxy boraneSodium boro hydride
Reactor
Centrifuge
Stage-8
Stage-8
Stage-8Sodium hydroxide
EthanolReactor
Centrifuge
Stage-9
Stage-9
Methanol to recovery
Ethanol to recovery
Stage-9Calcium chloride
WaterReactor
Centrifuge
Stage-10
Inorganic waste
Waste water
Final compound
SETRALINE HYDROCHLORIDE
The product is manufactured in four stages
Stage-1:
α -Naphthol when reacts with Dichloro Benzene in presence of Anhydrous Aluminum chloride produces
stage-1 compound. Methanol is the solvent used.
+Al Cl3MeOH
alpha naphtholC10H8O
Mol. Wt.: 144.2
dichloro benzeneC6H4Cl2
Mol. Wt.: 147C16H9Cl2O
Mol. Wt.: 289.2
OH
O
Cl
Cl
+ H2
HydrogenMol.Wt.:2
Stage-1
ClCl
Stage-2:
Stage-1 compound on condensation with Monomethylamine produces the stage-2 compound. Methanol is
used as the solvent. Reaction proceeds as follows.
O
Cl
Cl
+ H2O
WaterMol.Wt.:18
Stage-1
+ NH2 CH3
Methyl amineCH5N
Mol. Wt.: 31.1
MeOH
N
Cl
Cl
CH3
Stage-2C17H13Cl2N
Mol. Wt.: 302.2C16H10Cl2O
Mol. Wt.: 289.2
Stage-3:
Stage-3 compound is obtained when stage-2 product undergoes reduction reaction in acidic medium in
presence of Sodium boro hydride. Methanol is used as solvent.
N
Cl
Cl
CH3
Stage-2C17H13Cl2N
Mol. Wt.: 302.2
NaBH4
NH
Cl
Cl
CH3
HCl
C17H14Cl3NMol. Wt.: 338.7
Stage-3
MeOH+ HCl
Hydrochloricacid
Mol. Wt.: 36.5
Stage-4:
Finally pharma is obtained when stag-3 product is treated with D (-) Mandelic acid in Ethyl Acetate
medium. The compound is purified with carbon and water. The pharma is crystallized in Methanol.
NH
Cl
Cl
CH3
HCl
C17H14Cl3NMol. Wt.: 338.7
Stage-3
Ethyl AcetateD(-)Mandelic acid
NH
Cl
Cl
CH3
HCl
Sertraline HClC17H14Cl3N
Mol. Wt.: 338.7
FLOW CHART OF SERTRALINE HCl
Reactor
Stage-1
Stage-1:
alpha-NaptholDichloro Benzene
Aluminum chlorideMethanol
Methanol to recovery
Centrifuge
Stage-2Stage-1
MonomethylamineMethanol
Reactor
Centrifuge
Methanol to recovery
Water to recovery
Stage-2 product
Stage-2Sodium borohydride
Hydrochloric acidMethanol
Stage-3:
Reactor
Centrifuge
Methanol to recovery
Inorganic salt solutionWater
Stage-3 product
Stage-3Mandelic acid
Ethyl acetate
Stage-4:
Reactor
Centrifuge
Ethyl acetate to recovery
Final compound
SPARFLOXACIN
The compound can be prepared in seven stages.
Stage-1:
The reaction of ethyl penta fluoro benzoyl acetate with ethyl ortho formate in refluxing acetic anhydride in presence of acetic acid solvent medium forms the stage-1 compound.
F
F
F
F
F
O
COOEt
C11H7F5O3Mol. Wt.: 282.2
ethyl pentafluorobenzoylacetate
CH
OEt
EtO OEt
C7H16O3Mol. Wt.: 148
Triethyl ortho formate
+Ac2O
F
F
F
F
F
O
COOEt
CH
OEt
OEt
C16H17F5O5Mol. Wt.: 384
Stage-1
+ H3C OH
C2H6OMol. Wt.: 46.1
Ethanol
AcOH
Stage-2:
Stage-1 compound reacts with cyclopropyl amine in presence of ether solvent medium to form the amino methylene derivative as stage-2 product.
F
F
F
F
F
O
COOEt
CH
OEt
OEt
C16H17F5O5Mol. Wt.: 384
Reaction mass
NH2
+
C3H7NMol. Wt.: 57.1
Cyclopropyl amine
F
F
F
F
NH
O
COOEt
EtO
H3C OH
C2H6OMol. Wt.: 46.1
Ethanol
EtherF
+
C17H18F5NO4Mol. Wt.: 395
Stage-2
Stage-3:
Stage-2 compound undergoes cyclization by means of NaH in presence of Tetra hydro furan solvent medium to attain the stage-3 compound.
HF
Mol. Wt.: 20
F
F
F
F
NH
O
COOEt
EtO
H3C OH
C2H6OMol. Wt.: 46.1
Ethanol
F+
C17H18F5NO4Mol. Wt.: 395
Stage-2
NaH
THF
F
F
F
F
N
O
COOEt
C15H11F4NO3Mol. Wt.: 329
Stage-3
+
Hydrogen Fluoride
Stage-4:
Stage-3 compound reacts with benzyl amine by means of potassium carbonate in presence of acetonitrile solvent medium to obtain the stage-4 compound.
F
F
F
F
N
O
COOEt
C15H11F4NO3Mol. Wt.: 329
Stage-3
NH2
Benzyl amineC7H9N
Mol. Wt.: 107.
+K2CO3
Acetonitrile
NH
F
F
F
N
O
COOEt
HF+
HydrogenfluorideC22H19F3N2O3
Mol. Wt.: 416.4
Stage-4
Mol. Wt.: 20
Stage-5:
Stage-4 is deprotected by hydrogenation with H2 over Pd/C in ethanol solvent medium to form the stage-5 compound.
NH
F
F
F
N
O
COOEt
C22H19F3N2O3Mol. Wt.: 416.4
Stage-4
2 (H)+
Hydrogen
Mol. Wt.: 2
H2,Pd/C
NH2
F
F
F
N
O
COOEt
C15H13F3N2O3Mol. Wt.: 326.3
Stage-5
+
TolueneC7H8
Mol. Wt.: 92
Ethanol
CH3
Stage-6:
Stage-5 product undergoes acid hydrolysis with hot sulfuric acid yields the acid compound as stage-6.
NH2
F
F
F
N
O
COOEt
C15H13F3N2O3Mol. Wt.: 326.3
Stage-5
H2SO4H2O+
Water
Mol. Wt.: 18
NH2
F
F
F
N
O
COOH
C13H9F3N2O3Mol. Wt.: 298
Stage-6
C2H5OH+
EthanolC2H6O
Mol. Wt.: 46.1
Stage-7:
Stage-6 is finally condensed with cis-2, 6-dimethylpiperazine in presence of DMF solvent medium to obtain the final product.
NH2
F
F
F
N
O
COOH
C13H9F3N2O3Mol. Wt.: 298
Stage-6
DMFNH
HN
H3C CH3+
cis-2, 6-dimethylpiperazineC6H14N2
Mol. Wt.: 114.2
NH2
F
N
F
N
O
COOH
HN
H3C
CH3
C19H22F2N4O3Mol. Wt.: 392
Sparfloxacin
+ HF
HydrogenFluoride
Mol. Wt.: 20
FLOW CHART OF SPARFLOXACIN
ethyl penta fluoro benzoyl acetateTri ethyl ortho formate
Acetic anhydrideAcetic acid
Reactor
Centrifuge
Acetic acid to recovery
Waste ethanol
Stage-1
Stage-1
Stage-1Cyclopropyl amine
EtherReactor
Centrifuge
Ether to recovery
Waste ethanol
Stage-2 product
Stage-2
Stage-2Sodium hydride
THFReactor
Centrifuge
THF to recovery
Waste ethanol andHydrogen fluoride
Stage-3 product
Stage-3
Stage-3Benzyl amine
Potassium carbonateAcetonitrile
Reactor
Centrifuge
Acetonitrile to recovery
Hydrogen Fluoride
Stage-4
Stage-4
Stage-4Hydrogen Pressure
Pd/CEthanol
Reactor
Centrifuge
Ethanol to recovery
Hydrogen Fluoride
Stage-5 compound
Stage-5
Stage-5Water
Sulphuric acidReactor
Centrifuge Waste ethanol
Stage-6
Stage-6
Stage-6cis-2, 6-dimethylpiperazine
DMFReactor
Centrifuge Hydrogen Fluoride
Final compound
Stage-7
DMF to recovery
TERBINAFINE HYDROCHLORIDE
The product can be prepared in six stages.
Stage-1:
The Grignard reaction of 1-bromo naphthalene with Mg in presence of THF solvent medium and then reacts
with carbon dioxide with water gives the corresponding naphthoic acid as stsge-1 compound.
Br
C10H7BrMol. Wt.: 207.1
1-bromo naphthalene
+ Mg
MagnesiumMol. Wt.: 24
THF
MgBr
C10H7BrMgMol. Wt.: 231.4
1-Naphthyl magnesium bromide
CO2+
Carbon dioxideMol. Wt.: 44
+ H2O
Water
Mol.Wt.: 18
O OH
C11H8O2Mol. Wt.: 172.2
Stage-1
+Mg(OH)Br
Hydroxy magnesiumbromide
Mol. Wt.: 121
Stage-2:
STEP-A
Stage-1 compound reacts with SOCl2 in presence of MDC solvent medium forms the acid chloride
compound.
O OH
C11H8O2Mol. Wt.: 172.2
Stage-1
SOCl2+
Thionyl chlorideCl2OS
Mol. Wt.: 119
MDC
O Cl
C11H7ClOMol. Wt.: 190.6
Reaction mass
SO2
Sulphur dioxide
+ + HCl
Hydrochloric acidO2S
Mol. Wt.: 64.1ClH
Mol. Wt.: 36.5
STEP-B
The reaction mass formed in STEP-A reacts with methyl amine in presence of acetone solvent medium
forms the stage-2 compound.
+ MeNH2
OHN
CH3
C12H11NOMol. Wt.: 185
Stage-2
HCl
Hydrochloric acid
+
Methyl amineCH5N
Mol. Wt.: 31.1
O Cl
C11H7ClOMol. Wt.: 190.6
Reaction mass
Acetone
ClHMol. Wt.: 36.5
Stage-3:
Stage-2 product undergoes reduction with LiAlH4 in presence of THF solvent medium affords the
corresponding amine as stage-3 product.
OHN
CH3
C12H11NOMol. Wt.: 185
Stage-2
4 (H)+
HydrogenMol. Wt.: 4
LiAlH4
THF
HN
CH3
C12H13NMol. Wt.: 171
Stage-3
H2O+
Water
Mol.wt.: 18
Stage-4:
The condensation of propenal with tert-butyl acetylene by means of butyl lithium forms the stage-4
compound. The reaction proceeds as per the below equation.
CH+
C3H4OMol. Wt.: 56.1
Propenal Tert-butyl acetylene
CH3
BuLi
CH3
CHO
OH
C9H14OMol. Wt.: 138
Stage-4C6H10
Mol. Wt.: 82
Stage-5:
Stage-4 compound is rearranged with HBr in presence of acetone solvent medium forms the stage-5
product. The rearrangement takes place under the following equation.
CH
CH3
OH
C9H14OMol. Wt.: 138
Stage-4
HBr+ Acetone
CH
CH3
Br
C9H13BrMol. Wt.: 201
Stage-5Hydrogenbromide
Mol. Wt.: 81
H2O+
WaterMol. Wt.: 18
Stage-6:
Finally, the stage-3 product reacts with stage-5 product and also with hydrochloric acid in presence of
sodium carbonate affords Terbinafine hydrogen chloride. The reaction proceeds as per the below
equation.
CH
CH3
Br
C9H13BrMol. Wt.: 201
Stage-5
HN
CH3
C12H13NMol. Wt.: 171
Stage-3
+ Na2CO3HCl
Hydrochloric acid
Mol. Wt.: 36.5
+
N
CH3
CH
H3C CH3
CH3
Terbinafine HCl
. HCl
C21H26ClNMol. Wt.: 327.9
+HBr
Hydrobromicacid
Mol Wt.: 81
FLOW CHART OF TERBINAFINE HCl
1-bromo naphthaleneMagnesium
THFReactor
ReactorCarbon dioxixe
Water Hydroxy magnesium bromide
Stage-1
Spent solvent to recovery
Stage-1
Stage-1 productThionyl chloride
MDCReactor
Reactor
Stage-2
Stage-2
Solvent ml's to recoverySO2 & HCl emissions to scrubber
Methyl amineSpent acetone to recoveryHCl gas to scrubbing
Centrifuge
Stage-2Hydrogen
LiAlH4THF
Reactor
Stage-3
Stage-3
Centrifuge
Solvent ml's to recovery
Waste water
PropenalTert-butyl acetylene
Butyl lithiumReactor
Stage-4
Stage-4
Centrifuge
Stage-4Hydrogen bromide
AcetoneReactor
Stage-5
Stage-5
Centrifuge Waste water to recovery
Acetone to recovery
Stage-3Stage-5
Hydrochloric acidSodium carbonate
Reactor
Stage-6
Centrifuge Inorganic salt solution
Final product
Water
TRI CHLORO SALISYLIC ACID
The product can be manufactured in two stages.
Stage-1:
Salicylic acid undergoes chlorination in presence of acetic acid to form the stage-1 compound.
OH
COOH+
Salicylic acidC7H6O3
Mol. Wt.: 138
+2 Cl2
ChlorineCl4
Mol. Wt.: 141.8
CH3COOH
OH
C
Cl Cl
OH
O
C7H4Cl2O3Mol. Wt.: 207
3,5-dichloro salicylic acid
2 HCl
Hydrochloric acid
Mol. Wt.: 73
Stage-2:
3, 5-dichloro salicylic acid undergoes chlorination by passing chlorine gas in presence of oleum to form
the trichloro salicylic acid
+
OH
C
Cl Cl
OH
O
C7H4Cl2O3Mol. Wt.: 207
3,5-dichloro salicylic acid
OleumCl2
ChlorineCl2
Mol. Wt.: 70.9
OH
C
Cl Cl
OH
O
Cl
C7H3Cl3O3Mol. Wt.: 241.5
Trichloro salicylic acid
+ HCl
Hydrochloric acid
Mol. Wt.: 36.5
FLOW CHART OF TRICHLORO SALICYLIC ACID
Salicylic acidChlorine gaas
Acetic acidReactor
Centrifuge
Stage-1:
HCl gas to scrubber
Acetic acid MLs
Stage-1 product
Stage-1 productChlorine gas
OleumReactor
Centrifuge
Stage-2:
HCl gas to scrubber
Spent MLs
Final product
5-AMINO-2-HYDROXY BENZOIC ACID
Stage-1:
2-Chloro-5-Nitro Benzoic acid undergoes hydrolysis with sodium hydroxide in presence of water forms the stage-1 compound.
Cl
O2N
O OH
C7H4ClNO4Mol. Wt.: 201.6
2-Chloro-5-Nitro benzoic acid Sodium hydroxide
NaOH+
Mol. Wt.: 40
H2OOH
O2N
O OH
C7H5NO5Mol. Wt.: 183
Stage-1
NaCl+
Sodium chloride
Mol. Wt.: 58.5
Stage-2:
Stage-1 product undergoes hydrogenation with hydrogen pressure in presence of Raney nickel catalyst to form 5-Amino-2-Hydroxy Benzoic acid.
OH
O2N
O OH
C7H5NO5Mol. Wt.: 183
Stage-1
3 H2+
Hydrogen
Mol.Wt.: 6
Raney Ni/H2
OH
H2N
O OH
5-Amino-2-Hydroxy Benzoic acidC7H7NO3
Mol. Wt.: 153
+ 2 H2O
Water
Mol.Wt.: 36
FLOW CHART OF 5-AMINO-2-HYDROXY BENZOIC ACID
2-Chloro-5-Nitro Benzoic acidsodium hydroxide
waterReactor
Centrifuge Inorganic salt solution
Stage-1
Stage-1
Stage-1Raney nickle
Hydrogen pressureReactor
Centrifuge
Final product
Stage-2
Waste water to recovery
5-AMINO-2-DIBENZYLAMINO-1,6-DIPHENYL-HEX-4-EN-3-ONE
The product can be prepared in three stages.
Stage-1:
The reaction of L-phenyl alanine with benzyl bromide and potassium carbonate in ethanol forms the
stage-1 compound. The reaction undergoes as follows.
Ph
H2NOH
O
+
C9H11NO2Mol. Wt.: 165.2
Benzyl chlorideC21H21Cl3
Mol. Wt.: 379.8
L-Phenyl alanine
Ph
NO
O
Ph
Stage-1
+ 3 HCl
Hydrochloricacid
Mol. Wt.: 109.5
K2CO3Ethanol
Ph
Ph
H2C ClPh3
C30H29NO2Mol. Wt.: 435.6
Stage-2:
Stage-1 compound is condensed with acetonitrile by means of sodamide in presence of tetra hydro furan
solvent medium forms the stage-2 compound.
Ph
NO
O
Ph
Stage-1
Ph
Ph
H3C CN+
AcetonitrileC2H3N
Mol. Wt.: 41
NaNH2
THF Ph
NO
Ph
Ph
CN
C25H24N2OMol. Wt.: 368.5
Stage-2
HO Ph+
C7H8OMol. Wt.: 108
Benzyl alcoholC30H29NO2
Mol. Wt.: 435.6
Stage-3:
The reaction of stage-2 compound with benzyl magnesium chloride and water in presence of THF solvent
medium forms the required intermediate.
Ph
NO
Ph
Ph
CN
C25H24N2OMol. Wt.: 368.5
Stage-2
+
H2CPh MgCl
C7H7ClMgMol. Wt.: 151.9
Benzyl magnesium chloride
THF
NO
Ph
Ph
C33H35NOMol. Wt.: 461.6
Stage-3
+Mg(OH)Cl
+
Magnesium hydroxychloride
Mol. Wt.: 76.8
H2O
Water
Mol. Wt.: 18
FLOW CHART
L-phenyl alanineBenzyl chloride
Potassium carbonateEthanol
Reactor
Centrifuge
Ethanol solvent to recovery
Inorganic waste
Stage-1
Stage-1
Stage-1Acetonitrile
SodamideTetra hydro furan
Reactor
Centrifuge
THF solvent to recovery
Stage-2
Benzyl alcohol
Stage-2
Stage-2Benzyl magnesium chloride
WaterTHF
Reactor
Centrifuge
THF solvent to recovery
Stage-3
Inorganic waste
Final product
2-AMINO-6-CHLORO-3-NITRO PYRIDINE
Stage-1:
The compound can be prepared in two steps.
STEP-A:
2, 6-dichloro pyridine undergoes nitration with nitrating mixture i.e.; conc.HNO3 and conc.H2SO4 forms 2,
6-dichloro-3-nitro pyridine. The reaction proceeds as per the below equation.
N ClCl
2,6-dichloro pyridine
Conc. HNO3+
Nitric acidHNO3
Mol. Wt.: 63C5H3Cl2N
Mol. Wt.: 148
Conc. H2SO4+
Sulphuric acidH2O4S
Mol. Wt.: 98.1
N ClCl
NO2
C5H2Cl2N2O2Mol. Wt.: 193
2,6-dichloro-3-nitro pyridine Sulphuric acidH2O4S
Mol. Wt.: 98.1
+ H2O
WaterMol.Wt.:18
+H2SO4
STEP-B:
2, 6-dichloro-3-nitro pyridine on reaction with aqueous ammonia in the presence of isopropanol forms 2-
amino-6-chloro-3-nitro pyridine. The reaction proceeds as follows.
N ClCl
NO2
C5H2Cl2N2O2Mol. Wt.: 193
2,6-dichloro-3-nitro pyridine
+ Aq. NH3
AmmoniaH3N
Mol. Wt.: 17
IPAN NH2Cl
NO2
C5H4ClN3O2Mol. Wt.: 173.6
2-amino-6-chloro-3-nitro pyridine
+ HCl
Hydrochloric acid
Mol. Wt.: 36.5
FLOW CHART OF 2-AMINO-6-CHLORO-3-NITRO PYRIDINE
Stage-1
2,6-dichloro pyridineConc.H2SO4Conc.HNO3
Reactor
Quencher
Centrifuge Waste water to recovery
Aqueous ammoniaIso propyl alcohol Reactor
Centrifuge Waste HCl to recovery
Spent solvent to recovery
Filteration
Final product
4-CHLORO BUTYRYL CHLORIDE
Stage-1:
γ- Butyro lactone undergoes reduction in presence of Zinc Amalgam and Hydrochloric acid and then
reacts with Thionyl chloride to form 4-chloro butyryl chloride.
Thionyl chloride
SO
ClCl+
Cl2OSMol. Wt.: 119
O
+ 2 HCl
Gamma butyro lactone
O
C4H6O2Mol. Wt.: 86.1
2 Zn (Hg) +
Zinc amalgamZn
Mol. Wt.: 130.8
Hydrochloricacid
Mol. Wt.: 73
ClCl
C4H8Cl2Mol. Wt.: 127
4-chloro butyryl chloride
+ZnCl2
Zinc chlorideCl2Zn
Mol. Wt.: 136
+SO2
Sulfur dioxideO2S
Mol. Wt.: 64.1
+ZnO
Zinc oxideOZn
Mol. Wt.: 81.4
H2O
FLOW CHART
Gamma butyro lactoneZinc Amalgam
Hydrochloric acidThionyl chloride
Reactor
CentrifugeWater
SO2 to scrubber
ZnO & ZnCl2 to Waste Water
Final product