# US 8,772,491 B2 · Process for the preparation of solifenacin succinate

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- Number: US 8,772,491 B2
- Document ID: US8772491B2
- Status: Granted
- Kind: B2
- Application number: 13/261,551
- Filed: 2011-06-20
- Published: 2013-05-16
- Granted: 2014-07-08
- Earliest claimed: 2010-06-28
- Assignees: Aurobindo Pharma Ltd
- Applicants: Anand Gopalkrishna Kamat; Joseph Prabahar Koilpillai; Naga Trinadhachari Ganala; Venkata Lakshmi Upputuri; Venkata Balalji Boddu; Sivakumaran Meenakshisunderam
- Inventors: Anand Gopalkrishna Kamat; Joseph Prabahar Koilpillai; Naga Trinadhachari Ganala; Venkata Lakshmi Upputuri; Venkata Balalji Boddu; Sivakumaran Meenakshisunderam
- Web page: https://patentgrep.com/patent/US8772491B2

## CPC

- C07D 453/02: containing not further condensed quinuclidine ring systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The present invention relates to a process for the preparation of Solifenacin succinate by condensing a compound of formula (IVb) with (RS)-3-quinuclidinol, wherein, R represents methyl, ethyl, isopropyl; to produce a diastereomeric mixture of (1S)-3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylic acid (3RS)-1-azabicyclo[2.2.2]oct-3-yl ester, which is treated with succinic acid in a solvent or mixture of solvents to produce optically pure Solifenacin succinate, Formula (X).

## Claims

### Claim 1

A process for the preparation of Solifenacin succinate of formula (I);
which comprises:
(i) condensing a compound of formula (IVb) with (RS)-3-quinuclidinol of formula (Va),
wherein, R represents methyl, ethyl or isopropyl;
to produce a diastereomeric mixture of (1S)-3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylic acid (3RS)-1-azabicyclo[2.2.2]oct-3-yl ester,
(ii) treating the diastereomeric mixture of step (i) with succinic acid in a solvent or mixture of solvents to produce optically pure Solifenacin succinate (I).

### Claim 2 (depends on 1)

The process according to claim 1, wherein the process of step-(i) is carried out in the presence of a base in a solvent.

### Claim 3 (depends on 2)

The process according to claim 2, wherein the said base is inorganic base or organic base.

### Claim 4 (depends on 2)

The process according to claim 2, wherein the said solvent used in step-(i) is selected from a group comprising acetonitrile, hexane, heptane, methylcyclohexane, toluene, halogenated solvent ester ether or mixtures thereof.

### Claim 5 (depends on 1)

The process according to claim 1, wherein the solvent used in step-(ii) is selected from a croup comprising methanol, ethanol, isopropanol, ethyl acetate, and mixtures there-of.

### Claim 6 (depends on 1)

The process according to claim 1, wherein the process is carried out in a single step without isolating diastereomeric mixture of Solifenacin.

### Claim 7 (depends on 1)

The process according to claim 1, wherein the compound of formula (IVb) is prepared by a process comprising,
reacting (1S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline of formula (III) with an alkyl chloroformate in the presence of a solvent and a base,
to produce (1S)-alkyl 1-phenyl-1,2,3,4-tetrahydro-2-isoquinolinecarboxylate of formula (IVb).

### Claim 8 (depends on 7)

The process according to claim 7, wherein the alkyl chloroformate is selected from a group comprising ethyl chloroformate, methyl chloroformate and isopropyl chloroformate.

### Claim 9 (depends on 7)

The process according to claim 7, wherein the base used is selected from a group comprising triethylamine and trimethylamine.

### Claim 10 (depends on 7)

The process according to claim 7, wherein the solvent used is selected from a group comprising methylene chloride, 1,2-dichloroethane; toluene; ethyl acetate, and mixtures thereof.

### Claim 11 (depends on 3)

The process according to claim 3, wherein the inorganic base is selected from a group comprising sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, and mixtures thereof.

### Claim 12 (depends on 3)

The process according to claim 3, wherein the organic base is selected from a group comprising diethylamine, triethylamine, diisopropylethylamine, tert butylamine, pyridine, and mixtures thereof.

### Claim 13 (depends on 4)

The process according to claim 4, wherein the halogenated solvent is selected from a group comprising dichloromethane, dichloroethane, chloroform, and mixtures thereof.

### Claim 14 (depends on 4)

The process according to claim 4, wherein the ester is selected from a group comprising ethyl acetate, butyl acetate, isopropyl acetate, and mixtures thereof.

### Claim 15 (depends on 4)

The process according to claim 4, wherein the ether is selected from a group comprising diethyl ether, tetrahydrofuran, tert butyl methyl ether, and mixtures thereof.