WO2009138999A2 - Process for the preparation of paroxetine hydrochloride - Google Patents

Process for the preparation of paroxetine hydrochloride Download PDF

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Publication number
WO2009138999A2
WO2009138999A2 PCT/IN2009/000269 IN2009000269W WO2009138999A2 WO 2009138999 A2 WO2009138999 A2 WO 2009138999A2 IN 2009000269 W IN2009000269 W IN 2009000269W WO 2009138999 A2 WO2009138999 A2 WO 2009138999A2
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Prior art keywords
paroxetine
solvent
phenyl carbamate
formula
process according
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PCT/IN2009/000269
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French (fr)
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WO2009138999A3 (en
Inventor
Babu Rao Konudula
Saswata Lahiri
Govind Singh Rawat
Veera Narayana Bandlamudi
V. G. Phani Sharma
Debashish Datta
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Matrix Laboratories Ltd.
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Publication of WO2009138999A2 publication Critical patent/WO2009138999A2/en
Publication of WO2009138999A3 publication Critical patent/WO2009138999A3/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention relates to process for the preparation of Paroxetine hydrochloride, wherein Paroxetine N-phenyl carbamate is isolated as crystalline solid and further subjected to hydrolysis and converted into Paroxetine hydrochloride.
  • PAXIL is an orally administered psychotropic drug. It is hydrochloride salt of a phenylpiperidine compound chemically known as (-) trans isomer of 4-(p-fluorophenyl)-3S-(3 ,4 -methylenedioxy-phenoxymethyl)-piperidine hydrochloride. PAXIL is used for treatment of major depressive disorders, obsessive compulsive disorder, panic, social anxiety disorder and the like. Paroxetine hydrochloride is first claimed in US 4,007,196, and has the following structure of formula (I).
  • U.S. Patent No. 4,721,723 also prepares paroxetine N-phenyl carbamate, which is converted to paroxetine free base using potassium hydroxide pellets in toluene followed by addition of hydrochloric acid to give paroxetine hydrochloride salt.
  • U.S. Patent No. 6,686,473 discloses an alternative process for the preparation of Paroxetine.
  • N-methyl paroxetine is reacted with Phenylchloroformate using triethylamine followed by work-up and distillation to give Carbamate compound.
  • the resulting carbamate compound is subjected to hydrolysis reaction in the presence of potassium hydroxide in a mixture of toluene and n-butanol.
  • This process employs solvent mixtures and needs number of distillations to recover pure solvents. Hence this process is industrially not viable.
  • Main object of the present invention is to prepare crystalline Paroxetine-N-phenyl carbamate having N-methyl paroxetine impurity less than 0.01 %
  • Another object of the present invention is novel polymorphic form of Paroxetine-N-phenyl carbamate
  • Yet another object of the present invention is process for the preparation of crystalline Paroxetine N-phenyl-carbamate.
  • Main aspect of the present invention is to prepare crystalline Paroxetine-N-phenyl carbamate having N-methyl paroxetine impurity less than 0.01%.
  • Another aspect of the present invention is novel polymorphic form of Paroxetine-N-phenyl carbamate.
  • Yet another aspect of the present invention is to prepare process for the preparation of crystalline Paroxetine N-phenyl-carbamate.
  • Fig 1 X-ray diffraction pattern of crystalline Paroxetine-N-phenylcarbamate
  • the present invention relates to process for the preparation of Paroxetine hydrochloride, wherein Paroxetine N-phenyl carbamate is isolated as a crystalline solid and further subjected to hydrolysis and converted into Paroxetine hydrochloride.
  • the present invention relates to the isolation of crystalline paroxetine-N-phenylcarbamate of the formula (II)
  • Process for the preparation of Paroxetine-N-phenyl carbamate of formula (II) is having the N-methyl paroxetine impurity is less than 0.01% which comprises the steps of: a) reacting N-methyl paroxetine with Phenylchloroformate in a solvent b) isolating crystalline Paroxetine-N-phenyl carbamate and optionally crystallizing in a solvent
  • N-Methyl paroxetine is the starting material for the preparation of Paroxetine which is prepared according to the prior art procedures, like the one mentioned in US 4,007,196; US 4,902,801 or WO 00/26187.
  • N-methyl paroxetine is reacted with phenyl chloroformate in the presence of base in solvent medium.
  • the N-methyl paroxetine is dissolved in solvent is selected from dichloromethane, dichloroethane, ethyl acetate, toluene, cyclohexane and preferred solvent is toluene.
  • the condensation reaction is carried out in the presence of base, which is selected from monomethylamine, diethylamine, triethylamine, isopropyl amine, diisopropyl ethylamine preferably diisopropylethylamine.
  • reaction mass is cooled and washed with aqueous hydrochloric acid and water.
  • the organic layer is concentrated under reduced pressure to give residue, which is treated with a solvent selected from methanol, ethanol, n-propanol, isopropyl alcohol, n-butanol or mixtures thereof to give paroxetine-N-phenyl carbamate.
  • paroxetine-N-phenyl carbamate is optionally subjected to recrystallisation in a solvent selected from methanol, ethanol, n-propanol, isopropyl alcohol, n-butanol or mixtures thereof to give pure paroxetine-N-phenyl carbamate.
  • a solvent selected from methanol, ethanol, n-propanol, isopropyl alcohol, n-butanol or mixtures thereof to give pure paroxetine-N-phenyl carbamate.
  • the purity of paroxetine-phenylcarbamate is >99% preferably having N-methylparoxetine less than 0.01%.
  • paroxetine hydrochloride having the N-methyl paroxetine impurity less than 0.01%. Also Crystallinity of the carbamate compound is established.
  • PXRD pattern of the compound shows X-ray diffraction peaks having two theta values 13.35° ⁇ 0.2, 17.05° ⁇ 0.2, 17.79° ⁇ 0.2, 18.13° ⁇ 0.2, 18.79° ⁇ 0.2, 19.51° ⁇ 0.2, 19.86° ⁇ 0.2, 20.11° ⁇ 0.2, 20.97° ⁇ 0.2, 23.72° ⁇ 0.2, 24.02° ⁇ 0.2, 24.46° ⁇ 0.2, 24.74° ⁇ 0.2, 26.25° ⁇ 0.2, 28.36° ⁇ 0.2, 29.34° ⁇ 0.2, 30.09° ⁇ 0.2.
  • the above isolated crystalline Paroxetine-N-phenyl carbamate having N-methyl paroxetine less than 0.01% is subjected to hydrolysis reaction in the presence of base in solvent medium.
  • Base is selected from the group comprising alkali metal hydroxides, alkali metal hydroxide is selected from sodium hydroxide, and potassium hydroxide preferable base is potassium hydroxide.
  • Solvent selected for hydrolysis reaction is toluene, tetrahydrofuran, cyclohexane preferably toluene.
  • reaction is cooled and diluted with aqueous sodium hydroxide solution then separate the organic layer.
  • Organic layer is concentrated under pressure to get concentrated oil, which is dissolved in isopropyl alcohol and hydrochloric acid in IPA is added slowly over a period of time at 25-30° C to precipitate out paroxetine hydrochloride.
  • Crude Paroxetine hydrochloride is dissolved in solvent mixture at high temperatures. The clear solution was gradually cooled to room temperature wherein solid precipitates out which is later filtered and washed with chilled solvent. Wet material is dried at moderate temperature until desired moisture content is attained. Thus our product Paroxetine hydrochloride hemihydrate is obtained.
  • Example-I a) Paroxetine-N-Phenylcarbamate
  • N-methyl Paroxetine (100 g) and toluene (900 ml) were added into the RB flask.
  • Diisopropyl ethyl amine (7.6 gm) was added under stirring then heated the reaction mass to reflux temperature (110-112° C).
  • Phenyl chloroformate in toluene solution (57 gm PCF in 100ml toluene) was added and heated to reflux temperature.
  • reaction mass was washed with aqueous hydrochloric acid solution (100 ml) and extracted into toluene.
  • Organic layer was washed with sodium bicarbonate solution (50 gm in 1000 ml) then concentrated under reduced pressure to give residue.
  • Residue was treated with isopropyl alcohol (500 ml) to give paroxetine-N-phenylcarbamate.
  • Paroxetine-N-phenyl carbamate (125 gm) and toluene (1000 ml) were charged into the reaction mass.
  • Potassium hydroxide flakes (81.6 gm) was added and heated the reaction mass to reflux temperature (110° C).
  • mass was taken into aqueous sodium hydroxide solution (25gm of NaOH in 500ml DM water) and extracted into toluene.
  • Organic layer was separated and concentrated under reduced pressure to give residue.
  • Residue was dissolved in isopropyl alcohol (500 ml).
  • IPA IPA.
  • HCl (53.2 gm of HCl in 100 ml IPA) was charged to the above solution at 20-25° C. The resulting solution was stirred and filtered, washed with isopropyl alcohol to give paroxetine hydrochloride.
  • Paroxetine hydrochloride was suspended in isopropyl alcohol (500 ml) and DM water (20 ml) at (25-30° C). The reaction mass was heated to 70-75° C to get clear solution, then solution was cooled to 8-10° C. The separated solid was filtered, washed with chilled isopropyl alcohol (200 ml) and dried until desired moisture content is attained to yield Paroxetine hydrochloride hemihydrate (75-85 gm).
  • Paroxetine hydrochloride was suspended in isopropyl alcohol (500 ml) The reaction mass was heated to 70-75° C to get clear solution, then solution was cooled to 8-10° C. The separated solid was filtered, washed with chilled isopropyl alcohol (200 ml) and dried to yield Paroxetine hydrochloride anhydrous.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

The present invention relates to process for the preparation of Paroxetine hydrochloride, wherein Paroxetine-N-phenyl carbamate is isolated as a crystalline solid and further subjected to hydrolysis and converted into Paroxetine hydrochloride. According to our present invention N-methyl paroxetine is reacted with phenylchloroformate in the presence of base, solvent or optionally crystallizing in a solvent to give pure Paroxetine-N-phenyl carbamate. It is subjected to hydrolysis in the presence of base to give pharmaceutically acceptable paroxetine hydrochloride salt.

Description

PROCESS FOR THE PREPARATION OF PAROXETINE HYDROCHLORIDE
FIELD OF INVENTION:
The present invention relates to process for the preparation of Paroxetine hydrochloride, wherein Paroxetine N-phenyl carbamate is isolated as crystalline solid and further subjected to hydrolysis and converted into Paroxetine hydrochloride.
BACKGROUND OF THE INVENTION:
PAXIL (Paroxetine hydrochloride) is an orally administered psychotropic drug. It is hydrochloride salt of a phenylpiperidine compound chemically known as (-) trans isomer of 4-(p-fluorophenyl)-3S-(3 ,4 -methylenedioxy-phenoxymethyl)-piperidine hydrochloride. PAXIL is used for treatment of major depressive disorders, obsessive compulsive disorder, panic, social anxiety disorder and the like. Paroxetine hydrochloride is first claimed in US 4,007,196, and has the following structure of formula (I).
Figure imgf000002_0001
Paroxetine hydrochloride [Formula- 1]
US 4,007,196 patent discloses Paroxetine and a salt thereof with a pharmaceutically acceptable acid. The reaction involves condensation of N-methylparoxetine with Phenylchloroformate in dichloromethane at 0-5° C. The reaction product paroxetine-N- Phenyl carbamate is isolated from benzene. The carbamate intermediate so formed is hydrolyzed to Paroxetine using potassium hydroxide pellets in 2-methoxyethanol (methylcello solve) solvent. This solvent has a disadvantage that it participates in the reaction producing undesired trans-esterified intermediate which hydrolyses very slowly and forms a residue along with the hydrolysed product. Hence this process is industrially not feasible.
U.S. Patent No. 4,721,723 also prepares paroxetine N-phenyl carbamate, which is converted to paroxetine free base using potassium hydroxide pellets in toluene followed by addition of hydrochloric acid to give paroxetine hydrochloride salt.
U.S. Patent No. 6,686,473 discloses an alternative process for the preparation of Paroxetine. In this method N-methyl paroxetine is reacted with Phenylchloroformate using triethylamine followed by work-up and distillation to give Carbamate compound. The resulting carbamate compound is subjected to hydrolysis reaction in the presence of potassium hydroxide in a mixture of toluene and n-butanol. This process employs solvent mixtures and needs number of distillations to recover pure solvents. Hence this process is industrially not viable.
According to the prior art PXRD pattern of Paroxetine-N-phenyl carbamate is not disclosed and the purity of the same with comparison to N-methyl Paroxetine. There is a need to prepare crystalline Paroxetine-N-Phenyl carbamate having the N-methyl Paroxetine less than 0.01%.
OBJECT OF THE INVENTION:
Main object of the present invention is to prepare crystalline Paroxetine-N-phenyl carbamate having N-methyl paroxetine impurity less than 0.01 %
Another object of the present invention is novel polymorphic form of Paroxetine-N-phenyl carbamate
Yet another object of the present invention is process for the preparation of crystalline Paroxetine N-phenyl-carbamate. SUMMARY OF THE INVENTION
Main aspect of the present invention is to prepare crystalline Paroxetine-N-phenyl carbamate having N-methyl paroxetine impurity less than 0.01%.
Another aspect of the present invention is novel polymorphic form of Paroxetine-N-phenyl carbamate.
Yet another aspect of the present invention is to prepare process for the preparation of crystalline Paroxetine N-phenyl-carbamate.
DESCRIPTION OF THE DRAWINGS
Fig 1 : X-ray diffraction pattern of crystalline Paroxetine-N-phenylcarbamate
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to process for the preparation of Paroxetine hydrochloride, wherein Paroxetine N-phenyl carbamate is isolated as a crystalline solid and further subjected to hydrolysis and converted into Paroxetine hydrochloride.
The present invention relates to the isolation of crystalline paroxetine-N-phenylcarbamate of the formula (II)
Figure imgf000004_0001
Paroxetine Phenylcarbamate Formula-II
Process for the preparation of Paroxetine-N-phenyl carbamate of formula (II) is having the N-methyl paroxetine impurity is less than 0.01% which comprises the steps of: a) reacting N-methyl paroxetine with Phenylchloroformate in a solvent b) isolating crystalline Paroxetine-N-phenyl carbamate and optionally crystallizing in a solvent
N-Methyl paroxetine is the starting material for the preparation of Paroxetine which is prepared according to the prior art procedures, like the one mentioned in US 4,007,196; US 4,902,801 or WO 00/26187.
According to our present invention, N-methyl paroxetine is reacted with phenyl chloroformate in the presence of base in solvent medium. The N-methyl paroxetine is dissolved in solvent is selected from dichloromethane, dichloroethane, ethyl acetate, toluene, cyclohexane and preferred solvent is toluene. The condensation reaction is carried out in the presence of base, which is selected from monomethylamine, diethylamine, triethylamine, isopropyl amine, diisopropyl ethylamine preferably diisopropylethylamine.
According to our present invention, reaction mass is cooled and washed with aqueous hydrochloric acid and water. The organic layer is concentrated under reduced pressure to give residue, which is treated with a solvent selected from methanol, ethanol, n-propanol, isopropyl alcohol, n-butanol or mixtures thereof to give paroxetine-N-phenyl carbamate.
The above isolated paroxetine-N-phenyl carbamate is optionally subjected to recrystallisation in a solvent selected from methanol, ethanol, n-propanol, isopropyl alcohol, n-butanol or mixtures thereof to give pure paroxetine-N-phenyl carbamate. The purity of paroxetine-phenylcarbamate is >99% preferably having N-methylparoxetine less than 0.01%.
As per our present invention, paroxetine hydrochloride having the N-methyl paroxetine impurity less than 0.01%. Also Crystallinity of the carbamate compound is established.
PXRD pattern of the compound shows X-ray diffraction peaks having two theta values 13.35° ± 0.2, 17.05° ± 0.2, 17.79° ± 0.2, 18.13° ± 0.2, 18.79° ± 0.2, 19.51° ± 0.2, 19.86° ± 0.2, 20.11° ± 0.2, 20.97° ± 0.2, 23.72° ± 0.2, 24.02° ± 0.2, 24.46° ± 0.2, 24.74° ± 0.2, 26.25° ± 0.2, 28.36° ± 0.2, 29.34° ± 0.2, 30.09° ± 0.2.
Preparation of Paroxetine hydrochloride is schematically represented below:
Potassium hydroxide DiPA Toluene
Phenyl chloroformate Hydrochloric acid
Figure imgf000006_0003
Figure imgf000006_0001
Figure imgf000006_0002
N-Methyl Paroxetine Paroxetine Phenylcarbamate Paroxetine Hydrochloride Formula-l (Crude)
Figure imgf000006_0004
Paroxetine Hydrochloride (Pure)
As per our present invention, the above isolated crystalline Paroxetine-N-phenyl carbamate having N-methyl paroxetine less than 0.01%, is subjected to hydrolysis reaction in the presence of base in solvent medium. Base is selected from the group comprising alkali metal hydroxides, alkali metal hydroxide is selected from sodium hydroxide, and potassium hydroxide preferable base is potassium hydroxide.
Solvent selected for hydrolysis reaction is toluene, tetrahydrofuran, cyclohexane preferably toluene. After completion of hydrolysis, reaction is cooled and diluted with aqueous sodium hydroxide solution then separate the organic layer. Organic layer is concentrated under pressure to get concentrated oil, which is dissolved in isopropyl alcohol and hydrochloric acid in IPA is added slowly over a period of time at 25-30° C to precipitate out paroxetine hydrochloride. Crude Paroxetine hydrochloride is dissolved in solvent mixture at high temperatures. The clear solution was gradually cooled to room temperature wherein solid precipitates out which is later filtered and washed with chilled solvent. Wet material is dried at moderate temperature until desired moisture content is attained. Thus our product Paroxetine hydrochloride hemihydrate is obtained.
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.
The invention is further illustrated by the following non-limiting example.
Example-I: a) Paroxetine-N-Phenylcarbamate
N-methyl Paroxetine (100 g) and toluene (900 ml) were added into the RB flask.
Diisopropyl ethyl amine (7.6 gm) was added under stirring then heated the reaction mass to reflux temperature (110-112° C). Phenyl chloroformate in toluene solution (57 gm PCF in 100ml toluene) was added and heated to reflux temperature. After the completion of reaction, reaction mass was washed with aqueous hydrochloric acid solution (100 ml) and extracted into toluene. Organic layer was washed with sodium bicarbonate solution (50 gm in 1000 ml) then concentrated under reduced pressure to give residue. Residue was treated with isopropyl alcohol (500 ml) to give paroxetine-N-phenylcarbamate.
b) Paroxetine hydrochloride
Paroxetine-N-phenyl carbamate (125 gm) and toluene (1000 ml) were charged into the reaction mass. Potassium hydroxide flakes (81.6 gm) was added and heated the reaction mass to reflux temperature (110° C). After the completion of reaction, mass was taken into aqueous sodium hydroxide solution (25gm of NaOH in 500ml DM water) and extracted into toluene. Organic layer was separated and concentrated under reduced pressure to give residue. Residue was dissolved in isopropyl alcohol (500 ml). IPA. HCl (53.2 gm of HCl in 100 ml IPA) was charged to the above solution at 20-25° C. The resulting solution was stirred and filtered, washed with isopropyl alcohol to give paroxetine hydrochloride.
Dry weight: (120 gm)
c) Paroxetine hydrochloride (Hemihydrate)
Paroxetine hydrochloride was suspended in isopropyl alcohol (500 ml) and DM water (20 ml) at (25-30° C). The reaction mass was heated to 70-75° C to get clear solution, then solution was cooled to 8-10° C. The separated solid was filtered, washed with chilled isopropyl alcohol (200 ml) and dried until desired moisture content is attained to yield Paroxetine hydrochloride hemihydrate (75-85 gm).
d) Paroxetine hydrochloride (Anhydrous)
Paroxetine hydrochloride was suspended in isopropyl alcohol (500 ml) The reaction mass was heated to 70-75° C to get clear solution, then solution was cooled to 8-10° C. The separated solid was filtered, washed with chilled isopropyl alcohol (200 ml) and dried to yield Paroxetine hydrochloride anhydrous.
Dry weight: (75-85 gm)

Claims

We claim;
1. Paroxetine-N-phenyl carbamate of formula (II) having the N-methyl paroxetine impurity less than 0.01%.
2. Process for the preparation of Paroxetine-N-phenyl carbamate of formula (II) having the N-methyl paroxetine impurity less than 0.01% which comprising the steps of:
a) reacting N-methyl paroxetine with haloformate in a solvent, b) optionally crystallizing in a solvent and c) isolating Paroxetine-N-phenyl carbamate.
3. A process according to claim 2, wherein haloformate is selected from phenylchloroformate.
4. A process according to claim 2, wherein the solvent is selected from dichloromethane, dichloroethane, ethyl acetate, toluene, cyclohexane preferably toluene.
5. A process according to claim 2, wherein paroxetine-N-phenylcarbamate is isolated as crystalline solid.
6. A process according to claim 2, wherein the crystallizing solvent group is selected from C1-C4 alcohol, alcohol is selected from methanol, ethanol, isopropyl alcohol preferably isopropyl alcohol.
7. Paroxetine-N-phenyl carbamate of formula (II) having the similar PXRD pattern shown in figure-I.
8. Paroxetine-N-phenyl carbamate of formula (II) according to claim 7, wherein crystalline formula (II) is having the two theta values 13.35° ± 0.2, 17.05° ± 0.2, 17.79° ± 0.2, 18.13° ± 0.2, 18.79° ± 0.2, 19.51° ± 0.2, 19.86° ± 0.2,20.11° ± 0.2, (
20.97° ± 0.2, 23.72° ± 0.2, 24.02° ± 0.2, 24.46° ± 0.2, 24.74° ± 0.2, 26.25° ± 0.2, 28.36° ± 0.2, 29.34° ± 0.2, 30.09° ± 0.2.
9. Process for the preparation of Paroxetine hydrochloride comprising the steps of:
5 a) hydrolyzing Paroxetine-N-phenyl carbamate of formula (II) is having the N- methylparoxetine impurity is less than 0.01% in presence of base and solvent to obtain Paroxetine,
10 b) treating Paroxetine with hydrochloric acid and c) isolating Paroxetine hydrochloride.
10. A process according to claim 9a, wherein base is selected from alkali metal 15 hydroxide, alkali metal hydroxide is sodium hydroxide, potassium hydroxide preferably potassium hydroxide.
11. A process according to claim 9a, wherein solvent selected for hydrolysis reaction is dichloromethane, dichloroethane, ethyl acetate and toluene.
20
12. A process according to claim 9b, wherein hydrochloric acid is selected from gaseous hydrochloric acid, IPA. HCl or mixtures thereof;
13. A process according to claim 9b, wherein solvent used for the isolation of 25 Paroxetine hydrochloride selected from C1-C4 alcohol, alcohol selected from methanol, ethanol, isopropyl alcohol preferably isopropyl alcohol.
14. Process for the preparation of Paroxetine hydrochloride hemihydrate comprising the steps of:
30 a) hydrolyzing Paroxetine-N-phenyl carbamate of formula (II) is having the N- methyl paroxetine impurity is less than 0.01% in the presence of base, solvent to obtain Paroxetine,
b) treating Paroxetine with hydrochloric acid and 35 c) isolating Paroxetine hydrochloride hemihydrate. r »
15. Process for the preparation of Paroxetine hydrochloride anhydrous comprising the steps of:
a. hydrolyzing Paroxetine-N-phenyl carbamate of formula (I) is having the N- 5 methyl paroxetine impurity is less than 0.01% in the presence of base, solvent to obtain Paroxetine
b. treating Paroxetine with hydrochloric acid and 10 c. isolating Paroxetine hydrochloride anhydrous.
15
20
PCT/IN2009/000269 2008-05-06 2009-05-05 Process for the preparation of paroxetine hydrochloride WO2009138999A2 (en)

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IN1113/CHE/2008 2008-05-06
IN1113CH2008 2008-05-06

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007015262A2 (en) * 2005-04-25 2007-02-08 Sun Pharmaceutical Industries Limited A process for the preparation of (-)-trans-4-(p-fluorophenyl)-3-[[3,4-(methylenedioxy)phenoxy]methyl)]piperidine

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007015262A2 (en) * 2005-04-25 2007-02-08 Sun Pharmaceutical Industries Limited A process for the preparation of (-)-trans-4-(p-fluorophenyl)-3-[[3,4-(methylenedioxy)phenoxy]methyl)]piperidine

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