WO2013021343A1 - Procédé pour la résolution optique d'acide ()-3-(2-benzyloxy-5-bromophényl)-3-phénylpropionique - Google Patents

Procédé pour la résolution optique d'acide ()-3-(2-benzyloxy-5-bromophényl)-3-phénylpropionique Download PDF

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Publication number
WO2013021343A1
WO2013021343A1 PCT/IB2012/054015 IB2012054015W WO2013021343A1 WO 2013021343 A1 WO2013021343 A1 WO 2013021343A1 IB 2012054015 W IB2012054015 W IB 2012054015W WO 2013021343 A1 WO2013021343 A1 WO 2013021343A1
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WO
WIPO (PCT)
Prior art keywords
bromophenyl
benzyloxy
formula
phenylpropionic acid
hydroxyindane
Prior art date
Application number
PCT/IB2012/054015
Other languages
English (en)
Inventor
Shravan Kumar SINGH
Shyam Sunder Verma
Sourav HANDIQUE
Seema Ahuja
Kaptan Singh
Mohan Prasad
Sudershan Kumar Arora
Original Assignee
Ranbaxy Laboratories Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ranbaxy Laboratories Limited filed Critical Ranbaxy Laboratories Limited
Publication of WO2013021343A1 publication Critical patent/WO2013021343A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/42—Separation; Purification; Stabilisation; Use of additives
    • C07C51/487—Separation; Purification; Stabilisation; Use of additives by treatment giving rise to chemical modification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

Definitions

  • the present invention relates to a process for the preparation of fesoterodine and its salts.
  • Fesoterodine of Formula I is used to treat overactive bladder and is available as the fumarate salt. Fesoterodine rapidly de-esterifies to its active metabolite in the body, (R)-2- (3-diisopropylamino-l-phenylpropyl)-4-hydroxymethyl-phenol, which is a muscarinic receptor antagonist. Fesoterodine fumarate is chemically known as isobutyric acid 2-((R)- 3-diisopropylammonium- 1 -phenylpropyl)-4-(hydroxymethyl)phenyl ester hydrogen fumarate.
  • U.S. Patent No. 7,384,980 provides a process for the preparation of fesoterodine and its salts which involves the resolution of ( ⁇ )-3-(2-benzyloxy-5-bromophenyl)-3- phenylpropionic acid of Formula II with ephedrine hemihydrate in absolute ethanol at 0°C to obtain ephedrinium salt of R-(-)-3-(2-benzyloxy-5-bromophenyl)-3-phenylpropionic acid. This salt is recrystallized twice with boiling ethanol to obtain 97.6% e.e.
  • Ephedrine being a controlled substance, is difficult to obtain making the acquisition of ephedrine for use as a resolving agent a very complicated and time consuming process.
  • the present inventors have developed an advantageous process for the preparation of fesoterodine and its salts without the use of any narcotic resolving agent, such as, for example, ephedrine.
  • the present invention provides a simple, cost-effective and efficient process for the preparation of fesoterodine and its salts.
  • An aspect of the present invention provides a process for the resolution of ( ⁇ )-3-(2- benzyloxy-5-bromophenyl)-3-phenylpropionic acid of Formula II, comprising:
  • the compound, ( ⁇ )-3-(2-benzyloxy-5-bromophenyl)-3-phenylpropionic acid of Formula II is treated with (lR,2S)-(+)-cis-l-amino-2-hydroxyindane.
  • the reaction is carried out in the presence of an alcoholic solvent such as, for example, methanol, ethanol n-propanol, iso-propanol, butanol, pentanol, or a mixture thereof.
  • the reaction may be carried out at a temperature of about 5°C to about 100°C; preferably at about 15°C to about 70°C.
  • the reaction may be carried out for about 0.5 hour to about 100 hours;
  • the reaction may be facilitated by stirring the reaction mixture.
  • the salt of R-(-)-3-(2-benzyloxy-5-bromophenyl)-3-phenylpropionic acid (lR,2S)-(+)-cis-l-amino-2-hydroxyindane so obtained may be isolated from the reaction mixture by treatment with an antisolvent, extraction, precipitation, filtration, solvent evaporation, or a combination of these techniques.
  • the purification of the salt of R-(-)-3-(2-benzyloxy-5-bromophenyl)-3- phenylpropionic acid (lR,2S)-(+)-cis- l-amino-2-hydroxyindane may be carried using an alcoholic solvent; preferably, methanol, ethanol, n-propanol, iso-propanol, butanol, pentanol, or a mixture thereof.
  • the purification may be carried out at a temperature of about 5°C to about 100°C; preferably at about 15°C to 70°C.
  • the purification may be carried out for about 0.5 hour to about 100 hours; preferably for about 0.5 hour to about 20 hours.
  • the purification may be facilitated by stirring the reaction mixture.
  • the purified salt of R-(-)-3-(2-benzyloxy-5-bromophenyl)-3-phenylpropionic acid (1R, 2S)-(+)-cis-l-amino-2-hydroxyindane may be reacted with an organic acid or inorganic acid.
  • the organic acid may be acetic acid, tetra fluoro acetic acid or perchloric acid.
  • the inorganic acid may be hydrochloric acid or sulfuric acid.
  • the reaction may be carried out in presence of a chlorinated solvent, such as, for example, dichloromethane, chloroform, carbon tetrachloride, or a mixture thereof.
  • the R-(-)-3-(2-benzyloxy-5- bromophenyl)-3-phenylpropionic acid of Formula III is isolated from the reaction mixture by treatment with an antisolvent, extraction, precipitation, filtration, solvent evaporation, or a combination thereof.
  • the present method of synthesizing fesoterodine and its salts may further include exposing the compound of Formula III to thionyl chloride under suitable conditions to provide a compound of Formula IV.
  • Suitable conditions for obtaining the compound of Formula IV may include carrying out the reaction in N,N-dimethylformamide.
  • the reaction may be carried out at a temperature of about 30°C to about 120°C; preferably at about 45°C to about 60°C, for about 0.5 hour to about 24 hours; preferably for about 4 hours to about 7 hours.
  • the compound of Formula IV may be isolated from the reaction mixture by treatment with an antisolvent, extraction, precipitation, filtration, solvent evaporation, or a combination thereof.
  • the compound of Formula IV may further be treated with diisopropylamine under suitable conditions to provide a compound of Formula V.
  • Suitable conditions for obtaining the compound of Formula V include carrying out the reaction in a hydrocarbon solvent.
  • the hydrocarbon solvent may be selected from the group consisting of cycloheptane, cyclohexane, toluene and xylene.
  • the reaction may be carried out at a temperature of about 0°C to about 60°C; preferably at about 0°C to about 40°C, for about 1 hour to about 24 hours.
  • the compound of Formula V may be isolated from the reaction mixture by treatment with an antisolvent, extraction, precipitation, filtration, solvent evaporation, or a combination thereof.
  • the compound of Formula V may be reduced under suitable conditions to provide a compound of Formula VI.
  • Suitable conditions for obtaining the compound of Formula VI may include carrying out the reduction with metal hydride.
  • the metal hydride may be selected from the group consisting of sodium borohydride, lithium borohydride and diisobutylaluminum hydride.
  • the reduction may be carried out in ether solvent.
  • the ether solvent may include preferably diethyl ether, dimethyl ether, tetrahydrofuran, dioxane, or a mixture thereof.
  • the reaction may be carried out at a temperature of about 20°C to about 120°C; preferably at about 30°C to about 80°C, for about 1 hour to about 24 hours.
  • the compound of Formula VI may be isolated from the reaction mixture by treatment with an antisolvent, extraction, precipitation, filtration, solvent evaporation, or a combination thereof.
  • the compound of Formula VI may be exposed to ethyl halide and magnesium in the presence of solid carbon dioxide under suitable conditions to provide a compound of Formula VII.
  • the present process further includes contacting the compound of Formula VII with thionyl chloride under suitable conditions to provide a compound of Formula VIII.
  • Suitable conditions to obtain the compound of Formula VIII include carrying out the reaction in an alcoholic solvent.
  • the alcoholic solvent may be selected from the group consisting of methanol, ethanol, n-propanol, isopropanol, butanol, iso-butanol and pentanol, or a mixture thereof.
  • the reaction may be carried out at a temperature of about 0°C to about 100°C; preferably at about 5°C to about 80°C, for about 1 hour to about 24 hours; preferably for about 3 hours to about 7 hours.
  • the compound of Formula VIII may be isolated from the reaction mixture by treatment with an antisolvent, extraction, precipitation, filtration, solvent evaporation, or a combination thereof.
  • the compound of Formula VIII may be reduced under suitable conditions to a provide compound of Formula IX.
  • Suitable conditions to obtain the compound of Formula IX include carrying out the reduction with metal hydride.
  • the metal hydride may be selected from the group consisting of sodium borohydride, lithium borohydride and diisobutylaluminum hydride.
  • the reduction may be carried out in an ether solvent.
  • An ether solvent may include preferably diethyl ether, dimethyl ether, tetrahydrofuran, dioxane, or mixture thereof.
  • the reaction may be carried out at a temperature of about 20°C to about 100°C; preferably at about 20°C to about 50°C, for about 1 hour to about 24 hours.
  • the compound of Formula IX may be isolated from the reaction mixture by treatment with an antisolvent, extraction, precipitation, filtration, solvent evaporation, or a combination thereof.
  • the present process for synthesizing fesoterodine and its salts includes exposing the compound of Formula IX to hydrogenation under suitable conditions to provide a compound of Formula X.
  • Suitable conditions for hydrogenation of the compound of Formula IX may include carrying out hydrogenation in an autoclave.
  • the hydrogenation may be carried out in an alcoholic solvent.
  • the alcoholic solvent may be selected from the group consisting of methanol, ethanol, n-propanol, isopropanol, butanol, iso-butanol, pentanol, and a mixture thereof.
  • the reaction may be carried out at a temperature of about 20°C to about 80°C; preferably at about 25°C to about 40°C, for about 1 hour to about 24 hours; preferably for about 2 hours to about 7 hours.
  • the compound of Formula X may be isolated from the reaction mixture by treatment with an antisolvent, extraction, precipitation, filtration, solvent evaporation, or a combination thereof.
  • the present process for synthesizing fesoterodine and its salts may include exposing the compound of Formula X to isobutyryl chloride under suitable conditions to provide fesoterodine of Formula I and its salts. Suitable conditions include carrying out the reaction in a chlorinated solvent.
  • the chlorinated solvent may be selected from the group consisting of dichloromethane, chloroform and carbon tetrachloride.
  • the reaction may be carried out at a temperature of about 0°C to about 50°C; preferably at about 0°C to about 25°C, for about 1 hour to about 24 hours; preferably, for about 0.5 hour to about 3 hours.
  • the fesoterodine of Formula I may be isolated from the reaction mixture by treatment with an antisolvent, extraction, precipitation, filtration, solvent evaporation, or a combination thereof.
  • the fesoterodine of Formula I may be converted to its salts, such as, for example, the fumarate or hydrochloride salts.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention concerne un procédé pour la résolution d'acide (±)-3- (2-benzyloxy-5-bromophényl)-3-phénylpropionique de formule II, comprenant les étapes de : a) résolution d'acide (±)-3-(2-benzyloxy-5-bromophényl)-3-phénylpropionique de formule II (II) X = bromo (II) avec le (1R,2S)-(+)-cis-1-amino-2-hydroxyindane ; et b) isolement d'acide R-(-)-3-(2-benzyloxy-5-bromophényl)-3-phénylpropionique de formule III à partir du mélange de réaction de celui-ci.
PCT/IB2012/054015 2011-08-05 2012-08-06 Procédé pour la résolution optique d'acide ()-3-(2-benzyloxy-5-bromophényl)-3-phénylpropionique WO2013021343A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN2211DE2011 2011-08-05
IN2211/DEL/2011 2011-08-05

Publications (1)

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WO2013021343A1 true WO2013021343A1 (fr) 2013-02-14

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996036584A1 (fr) * 1995-05-18 1996-11-21 Sepracor, Inc. Procede permettant le dedoublement d'acides chiraux a l'aide de 1-aminoindan-2-ols
EP0937710A1 (fr) * 1998-02-16 1999-08-25 Ajinomoto Co., Inc. Procédé de préparation d'un dérivé de l'acide phénylpropionique optiquement actif
US7384980B2 (en) 1998-05-12 2008-06-10 Schwarz Pharma Ag Derivatives of 3,3-diphenylpropylamines

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996036584A1 (fr) * 1995-05-18 1996-11-21 Sepracor, Inc. Procede permettant le dedoublement d'acides chiraux a l'aide de 1-aminoindan-2-ols
EP0937710A1 (fr) * 1998-02-16 1999-08-25 Ajinomoto Co., Inc. Procédé de préparation d'un dérivé de l'acide phénylpropionique optiquement actif
US7384980B2 (en) 1998-05-12 2008-06-10 Schwarz Pharma Ag Derivatives of 3,3-diphenylpropylamines

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
ISABELLE GALLOU ET AL: "cis -1-Amino-2-indanol in Drug Design and Applications to Asymmetric Processes", CHEMICAL REVIEWS, vol. 106, no. 7, 1 July 2006 (2006-07-01), pages 2843 - 2874, XP055045029, ISSN: 0009-2665, DOI: 10.1021/cr050970a *

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