1. A racemization process for the preparation of 1-phenyl-l, 2,3,4-tetrahydroisoquinoline of a compound of Formula (I), the process comprising: (a) providing a material comprising a suitable diastereomeric salt of (L/?)-l-phenyl-l,2,3,4-tetrahydroisoquinoline (V); (b) reacting the material with one or more bases, optionally in the presence of one or more suitable solvents to form (17?)-l-phenyl-l,2,3,4-tetrahydroisoquinoline of a compound of Formula (IB); (c) reacting the (L/?)-I-phenyl-l,2,3,4-tetrahydroisoquinoline of the compound of Formula (IB) with Halogenating reagents in the presence of suitable base in one or more suitable solvents to obtain a compound of Formula (IV), Wherein X is chlorine or bromine or iodine etc; d) hydrolyzing the compound of Formula (IV) in the presence of base or acids in one or more suitable solvents to obtain the 1 -phenyl- 1,2,3,4-tetrahydroisoquinoline racemate of the compound of Formula (I).

2. The process as claimed in claim 1, step (a), wherein the material further comprises (17?)-l-phenyl-l,2,3,4-tetrahydroisoquino!ine of the compound of Formula (IB) such that R:S ratio of the starting mixture is about R:S ratio is about in the range of 10:20 to 60:40, preferably 50:50.

3. A process for the preparation of (^)-2-Chloro-l52,354-tetrahydro-l-phenylisoquinoline compound of formula (IVA):

3. The process as claimed in claim 1, step (b), wherein the suitable base is selected from sodium carbonate, potassium carbonate, sodium bicarbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, ammonia ( or) organic bases like triethyl amine, pyridine, disopropylethyl amine, piperidine, morpholine or mixtures thereof.

5. The process as claimed in claim 1, step (b), wherein the suitable solvent is selected from alcohols, esters, chlorinated solvents, nitriles, hydrocarbons, ketones, aprotic polar, water, or their suitable mixtures.

6. The process as claimed in claim 1, step (c), wherein the suitable Halogenating reagent is selected from N-Chlorosuccinimide, N-Bromosuccinimide, PGs, POCI3, SOCI2, Sulfuryl chloride etc.

7. The process as claimed in claim 1, step (d), wherein the acid is selected inorganic acids such as HC1, H2S04, HBr, HN03 (or) organic acids such as HCOOH, CH3COOH, CH3CH2COOH; lower haloalkyl acid such as CF3COOH, dichloroacetic acid; phosophoric acid, lower alkyl phosphonic acid such as methylphosphonic acid, phenylphosphonic acid, BF3.0Et2 or mixture thereof.

8. A recycling process for the (R) enriched enantiomer of 1-phenyl-1,2,3,4-tetrahydroisoquinoline comprises treatment of diastereomeric salt of (lTJ)-l-phenyl-1,2,3,4-tetrahydroisoquinoline with one or more suitable organic or inorganic base.

9. According to preceding claimed processes are used for the preparation of Solifenacin or a salt thereof.

A PROCESS FOR THE PREPARATION OF SOLIFENACIN SUCCINATE FIELD OF THE INVENTION

The invention relates to processes for the preparation of Solifenacin or a salt thereof. In particular, it relates to a process for the recovery and racemization of (LR)-phenyl-1,2,3,4-tetrahydroisoquinoline to obtain (LS)-l-phenyl-l, 2, 3, 4-tetrahydroisoquinoline in high chemical and chiral purity, which is particularly useful for the preparation of Solifenacin or a salt thereof.

BACKGROUND OF THE INVENTION

l-phenyl-l,2,3,4-tetrahydroisoquinoline of the following Formula (I), is a key intermediate for the preparation of (37?)-azabicyclo[2.2.2]oct-3-yl (LS)-l-phenyl-3,4-dihydroisoquinoline-2-(l//)-carboxylate, also known as Solifenacin or YM-905 (in its free base form) and YM-67905 (in its succinate form).

Solifenacin succinate is available in the market in the tablet form under the trade name, Vesicare®. It is a urinary antispasmodic of the anticholinergic class. It is used in the treatment of overactive bladder with urge incontinence and acts as a selective antagonist to the M (3) receptor. [Chilman-Blair, Kim et.al, Drugs Of Today, 40(4):343-353, 2004].

The compound (3i?)-azabicyclo[2.2.2]oct-3-yl-(15)-l-phenyI-3,4dihydroisoquinoline-2' (lH)-carboxylate was first disclosed in U.S. Patent No. 6,017,927 ('the *927 patent") by Yamanouchi Pharmaceuticals. The '927 patent also discloses compounds of the following general Formula:

A specific method for the preparation of (3i?)-azabicycIo[2.2.2]oct-3-yl-(lS)-l-phenyI-3,4-dihydroisoquinoline-2-(l//)-carboxyiate or a salt thereof disclosed in the '927 patent, is depicted in the following

In general, two processes for synthesizing Solifenacin are known in the art, which use the following key intermediates or their derivatives as starting materials.

The '927 patent describes a process using these two intermediates (II) and (IA) shown in the above scheme 1.

Another process for the synthesis of solifenacin is disclosed by Mealy, N., et al. in Drugs of Future, 24(8): 871-874(1999).

The optical resolution of 1-phenyl-l, 2, 3, 4-tetrahydroisoquinoline is disclosed in Monatshefte fur chemie, vol. 53-54:956-962(1929) to obtain (lS)-phenyl-l,2,3,4-tetrahydroisoquinoIine i.e. intermediate IA . The procedure involves addition of a solution of (D)-tartaric acid in water to free base. A similar method with slight modification is disclosed in J. Chem. Soc. Perkin. Trans I, (4), 869-73 (1988) and also in Naito et al. in J. Med. Chem. 48(21): 6597-6606 (2005) with modified method using ethanol for addition of tartaric acid and recrystallization from water to obtain (lS)-phenyI-l,2,3,4-tetrahydroisoquinoline is disclosed. The process involves multiple steps of crystallization.

International Publication (PCT) WO 2008019055 discloses a process for optical resolution of 1-phenyl-l,2,3,4-tetrahydroisoquinoline (I).

U.S. Publication No. 20080114029 discloses a new crystalline form I of (S)-(+)-l-phenyI-1,2,3,4-tetrahydroisoquinoline and process for its preparation. The process discloses combining (S)-(+)-l-phenyl-l,2,3,4-tetrahydroisoquinoline tartarate in water and an inorganic base in THF or toluene as a solvent.

International Publication (PCT) WO 2008011462 discloses processes for the preparation of (3i?)-azabicyclo [2.2.2]oct-3-yI (lS)-l-phenyl-3,4-dihydroisoquinoline-2-(l//)-carboxylate by reacting a compound of Formula (III), wherein R= (C1-C4) alkyl, aryl, or aralkyl group. Further, it discloses the recovery of l-phenyl-l,2,3,4-tetrahydroisoquinoline (I) from the mother liquor generated during the resolution stage in the preparation of (lS)-phenyl-I,2,3,4-

tetrahydroisoquinoline (IA) . The drawback of this process is that it requires high temperature and longer reaction time for completion of the reaction and also suffers from the problems like, low yield and tedious work-up.
However, there exists a need in the art for the recovery of racemic l-phenyl-l,2,3,4-tetrahydro isoquinoline (I) /which gives high yield and also suitable for large scale preparation. The process disclosed herein for the recovery of the racemic 1-phenyl-l, 2,3,4-tetrahydroisoquinoIine (I) improves the overall yield and makes this process cost effective.

SUMMARY OF THE INVENTION

In one aspect there is provided a racemization process for the preparation of 1 -phenyl-1,2,3,4-tetrahydroisoquinoline (I) racemate. The process includes:

(a) providing a material comprising (li?)-l-phenyl-l,2,3,4-tetrahydroisoquinoline of a compound of Formula (IB);

(b) reacting the material of step-a with suitable Chlorinating agent in the presence of a suitable base in one or more suitable solvents to obtain a compound of Formula (IV),

wherein X is chlorine or Bromine or iodine etc;

(c) hydrolyzing the compound of Formula (IV) in the presence of suitable bases or acids in one or more suitable solvents to obtain the l-phenyl-l,2,3,4-tetrahydroisoquinoline racemate of the compound of Formula (I).

In another aspect there is provided a racemization process for the preparation of l-phenyl-1,2,3,4-tetrahydroisoquinoline racemate from a diastereromeric salt of (l#)-l-phenyl-l,253,4-tetrahydroisoquinoline of a compound of Formula (V):

The process includes: (a) providing a material comprising a suitable diastereromeric salt of (17?)-l-phenyl-l,2,3,4-tetrahydroisoquinoIine (V); (b) reacting the material with base, optionally in the presence of one or more suitable solvents to form (172)-l-phenyl-l?2,354-tetrahydroisoquinoline of a compound of Formula (IB); (c) reacting the (17?)-l-phenyl-l52,3,4-tetrahydroisoquinoIine of the compound of Formula (IB) with suitable halogenating reagents in the presence of suitable

bases in one or more suitable solvents to obtain a compound of Formula (IV), wherein X is as defined above; and (d) hydrolyzing the compound of Formula (IV) in the presence of base or acid in one or more suitable solvents to obtain the l-phenyl-l,2,3,4-tetrahydroisoquinoline racemate of the compound of Formula (I).

In another aspect there is provided a process for the preparation of (lS)-l-phenyl-l,2,3,4-tetrahydroisoquinoline in high chemical and chiral purity or a pharmaceutical^ acceptable salt thereof. The process includes the steps of : (a) providing a material comprising a suitable diastereromeric salt of (l^)-l-phenyl-l,2,3,4-tetrahydroisoquinoline (V); (b) reacting the material with base, optionally in the presence of one or more suitable solvents to form (Lfl)-l-phenyl-1,2,3,4-tetrahydroisoquinoline of a compound of Formula (IB); (c) reacting the (17?)-l-phenyl-1,2,3,4-tetrahydroisoquinoline of the compound of Formula (IB) with suitable halogenating agent in the presence of suitable base in one or more suitable solvents to obtain a compound of Formula (IV), wherein X is as defined above; and (d) hydrolyzing the compound of Formula (IV) in the presence of base or acid in one or more suitable solvents to obtain the l-phenyl-1,2,3,4-tetrahydroisoquinoline racemate, which can be further resolved by using suitable resolving agents in a suitable solvent to get (lS)-l-phenyl-l,2,3,4-tetrahydroisoquinoIine.

In another aspect provided a process for the preparation of solifenacin or salt thereof The process includes the steps: (a) The (LS)-I-phenyl-l,2,3,4-tetrahydroisoquinoIine react with aryl or its chloroformate, substituted aryl carbonate or chloroformate, heteroaryl carbonate or chloroformate, substituted heteroaryl carbonate or its chloroformate in suitable solvents and suitable base to obtain the compound of Formula (VI), wherein Rl is alkyl, aryl, substituted aryl, substituted alkyl, or substituted halo alkyl group, (b) The compound of Formula (V) is further react with (R)-3-quinuclidinol in presence of a suitable base in suitable solvent to obtain (+)-(lS,3!R)-quinuclidin-3'-yl l-phenyl-l,2,3,4-tetrahydro-isoquinoline-2-carboxylate.

The details of one or more embodiments of the inventions are set forth in the description below. Other features, objects and advantages of the inventions will be apparent from the description and claims.

DETAILED DESCRIPTION OF THE INVENTION

The inventors have developed a process for recycling the (R) enriched enantiomer of l-phenyl-1,2,3,4-tetrahydroisoquinoline, which is obtained from resolution of l-phenyI-l,2,3,4-tetrahydro isoquinoline using suitable resolving agents, to produce more of the (5) enantiomers. The 1 -phenyl- 1,2,3,4-tetrahydroisoquinoline is commercially available. In particular, it may be prepared by a method disclosed in'jMC 1989, 32, 1242-1248 and JMC 2005, 48, 6597-6606.

Chirally enriched (172)-l-phenyl-l,2,3,4-tetrahydroisoquinoline of Formula (IB) may be isolated after treating the diastereromeric salt of (li?)-l-phenyl-l,2,3,4-tetrahydroisoquinoline of Formula (V) using suitable base in the presence of one or more suitable solvents. The diastereromeric salt of (li?)-l-phenyl-l?2,3,4-tetrahydroisoquinoline of Formula (V) is formed with suitable resolving agents, which in turn is obtained from the mother liquor (filtrate) after resolution of 1-phenyl-1,2,3,4-tetrahydroisoquinoline (I). It can be racemized to obtain the racemic I-phenyl-1,2,3,4-tetrahydroisoquinoline of Formula (I),which can be further resolved by using suitable resolving agents in a suitable solvent to get (15)-l-phenyI-l,2,3,4-tetrahydroisoquinoline in high chemical and chiral purity. This compound is a key intermediate for the synthesis of the drug solifenacin, (37?)-azabicyclo[2.2.2]oct-3-yl (15)-l-phenyl-3,4-dihydroisoquinoline-2-(l//)-carboxylate.

The inventors have developed a process for the racemization of (L/?)-I-phenyl-l,2,3,4-tetrahydro isoquinoline of Formula (IV). The process includes isolating a chirally enriched (li?)-l-phenyl-1,2,3,4-tetrahydroisoquinoline of a compound of Formula (IB),

from an aqueous solution of a diastereromeric salt of (17?)-l-phenyl-l,2,3,4-tetrahydro isoquinoline (V), alternatively from the solution of diastereromeric salt of (IR)-l-phenyl-l,2,3,4-tetrahydroisoquinoline (V) using a suitable base optionally in the presence of one or more suitable solvents;

. reacting the (L/?)-l-phenyl-l,2,3,4-tetrahydroisoquinoline (IB) with suitable halogenating reagent in the presence of a suitable base in one or more suitable solvents to obtain a compound of Formula (IV), wherein X is chlorine or Bromine or iodine etc; and
hydrolyzing the N-substituted l-phenyl-l,2,3,4-tetrahydroisoquinoline of the compound of Formula (IV) in the presence of. suitable base or acid in one or more suitable solvents at a suitable temperature to obtain racemic l-phenyl-l,2,3,4-tetrahydroisoquinoline (I).
In general, the (17?)-l-phenyI-l,2,3,4-tetrahydroisoquinoline of Formula (IB) may be reacted with a suitable halogenating reagents selected from N-Chlorosuccinimide, N-Bromosuccinimide, PC15, POCI3, SOCI2, Sulfuryl chloride, in the presence of a suitable base in a suitable solvent to obtained compound of formula (IV).

Suitable solvents which can be used include one or more of alcohols like methanol, ethanol, isoprppanol, butanol, 1,2-dimethoxy ethanol, 2-methoxy ethanol, 2-ethoxy ethanol, isoamyl alcohol and ethylene glycol; esters like ethyl acetate and isopropyl acetate; chlorinated solvents like chloroform and dichloromethane; nitriles like acetonitrile; hydrocarbons like toluene, xylene

and chlorobenzene; ketones like acetone, methyl ethyl ketone; ethers like diethyl ether, 1,4-dioxane, DIPE, MTBE, THF; aprotic polar solvents such as DMF, DMSO, DMA or their suitable mixtures.

Suitable bases which can be used include one or more of NaHCCh, Na2CC>3, K2C03, LiOH, NaOH, KOH and the like. Suitable organic base is selected from ammonia, C(l-5) alkyl amines, C(l-5) substituted alkyl amines such as triethylamine, diisopropylamine, disopropylethyl amines, heterocyclic saturated or unsaturated base such as pyridine, piperidine, morpholine and the like or mixtures thereof.

The hydrolysis of N-substituted l-phenyl-l,2,3,4-tetrahydroisoquinoIine of the compound of Formula (IV) may be carried out in the presence of suitable base or suitable acid in one or more suitable solvents at a suitable temperature to obtain racemic l-phenyl-1,2,3,4-tetrahydroisoquinoline of the compound of Formula (I).

The hydrolysis may be carried out using reagents which assist in the cleavage of the N-substituted group to obtain l-phenyl-l,2,3,4-tetrahydroisoquinoline of the compound of Formula (IV) by standard techniques reported in the literature, to provide the compound of Formula (I).Suitable acid which can be used for the hydrolysis may include one or more of inorganic acids such as HCI, H2SO4, HBr, HNC^, and the like; organic acids selected from lower alkyl acid such as HCOOH, CH3COOH, CH3CH2COOH; lower haloalkyl acid such as CF3COOH, dichloroacetic acid; phosphoric acid, lower alkyl phosphonic acid such as methylphosphonic acid, phenylphosphonic acid, BF3.0Et2, and the like or mixtures thereof.

The (lS)-l-phenyl-l,2,3,4-tetrahydroisoquinolinecompound of formula (IA) react with aryl carbonate or its chloroformate, substituted aryl carbonate or chloroformate, heteroaryl carbonate or chloroformate, substituted heteroaryl carbonate or its chloroformate such as ethyl chloroformate, 4-nitrophenyl chloroformate, 2-dipyridyl carbonate to obtain the compound of Formula (VI), wherein R' is alkyl, aryl, substituted aryl, substituted alkyl, or substituted halo alkyl group.

The compound of Formula (VI) react with (i?)-3-quinuclidinol in presence of a base in suitable solvent to obtain (+)-(lS',37?)-quinuclidin-3,-yl 1-phenyl-l,2,3,4-tetrahydro-isoquinoline-2-carboxylate.

Suitable solvents which can be used for may include one or more of alcohols, for example, methanol, ethanol, isopropanol, butanol, 1,2-dimethoxy ethanol, 2-methoxy ethanol, 2-ethoxy ethanol, isoamyl alcohol and ethylene glycol; esters, for example, ethyl acetate and isopropyl acetate; chlorinated solvents, for example, chloroform and dichloromethane; nitriles, for example, acetonitrile; hydrocarbons, for example, toluene, xylene and chlorobenzene; ketones, for example, acetone, methyl ethyl ketone; ethers, for example, diethyl ether, 1,4-dioxane, DIPE, MTBE, THF; aprotic polar solvents such as DMF, DMSO, DMA; water or their suitable mixtures.

Suitable bases, which can be used for may include one or more of NaHC03, Na2CC>3, K2CO3, LiOH, NaOH, KOH and the like. Suitable organic base is selected from ammonia, CI-5 alkyl amines, CI-5 substituted alkyl amines such as triethylamine, disopropylamines, disopropylethyl amines, heterocyclic saturated or unsaturated base such as pyridine, piperidine, morpholine and the like or mixtures thereof.

The present invention is further illustrated by the following examples which are provided merely to be exemplary of the invention and do not limit the scope of .the invention. 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.

Examples:

Example 1: Preparation of (/f)-2-Chloro-l,2,3.4-tetrahydro-l-phenylisoquinoIine

To a dry 1000 mL three neck flask, enantiomerically enriched (1R)-1 -phenyl-1,2,3,4-tetrahydroisoquinoline (100 g), dichloromethane (500 mL) and triethylamine (10.22 g) were charged at 20-25°C temperature. The reaction mixture was cooled to 0 to 5°C. Then N-Chlorosuccinimide (70.12 g) was added drop by drop over a period of 1 h at 0 to 5 °C. The reaction mixture was warmed to room temperature and stirred for 4-5 h at room temperature. To the reaction mixture, water and dichloromethane were added. It was transferred into a separating funnel. The organic layer was separated and washed with 100 ml of Dichloromethane. The organic layer was dried over anhydrous sodium sulfate. The solvent was then distilled out completely under a reduced pressure to obtain enantiomerically enriched N(7?)-2-Chloro-l,2,3.4-tetrahydro-1 -phenylisoquinoline as a liquid.

Example 2: Preparation of l-phenyl-l,2,3,4-tetrahydroisoquinoline

To a dry 1000 mL three neck flask, enantiomerically enriched (7?)-2-Chloro-1,2,3.4-tetrahydiro-l-phenylisoquinoline (103.5g), 35 % cone. HC1 and 85 % aq. phosphoric acid) were charged at 25-50 °C. The reaction mixture was heated to 95 to 100 °C and stirred for 8-10 h and subsequently cooled to room temperature. The reaction mixture was transferred into a separating funnel and subsequently washed with toluene and ethyl acetate. The aqueous layer was collected and was basified with 40 % aq. NaOH solution up to 9-10 pH at room temperature. The solid was precipitated and was extracted in ethyl acetate. The extract was washed with water and dried over anhydrous sodium sulfate. The solvent was then distilled out completely under a reduced pressure to obtain l-phenyl-l,2,3,4-tetrahydroisoquinoline

Example 3: Preparation of (5)- Ethyl l-phenyl-l,2,3,4-tetrahydroisoquinoIine-2-caboxyIate

To a dry, 25 mL round bottom flask was charged (S)-l-phenyl-l,2,3,4-tetrahydro-isoquinoline (1 g) and toluene (6 mL) at room temperature (RT). It was cooled to 5 to 10 °C and ethyl chloroformate (0.52 g) was added slowly into the reaction mixture. It was heated to reflux temperature and stirred till completion of the reaction. Distilled out the solvent at reduced pressure. To the residue dil. Aq. HC1 and dichloromethane were added. It was transferred into a separating funnel. Organic layer was collected. It was washed with saturated. Sodium bicarbonate solution. Organic layer was collected and dried over anhydrous. Sodium sulphate. It was concentrated under reduced pressure to obtain Ethyl (S)-l-phenyl-l,2,3,4-tetrahydro-isoquinoline-2-carboxyIate.

Example 4 Preparation of (+)-(!S,3,R)-quinuclidin-3,-yI l-phenyI-1.2.3.4-tetrahydro-isoquinoline-2-carboxylate (Solifenacin)

To a cooled solution of freshly prepared sodium methoxide (4.2 g), (R)-3-quinuclidinol (10 g) was added under N2 atmosphere. It was stirred at 5-30 °C for 30 min Distilled out the solvent at reduced pressure. To the semi-solid mass dry toluene was added and reaction mixture was heated to reflux temperature and stirred for 1 to 2h. The reaction mixture was cooled to 60-70 °C (S)-Ethyl l-phenyl-l,2,3,4-tetrahydroisoquinoline-2-caboxylate (20 g) dissolved in dry toluene (160 mL) and dry DMF (25 mL) were added. It was again heated to reflux temperature and stirred for 10 to 12 h while distilling off toluene to remove ethanol after every 15 min. intervals with addition of fresh quantity of dry toluene. It was cooled to room temperature. The (+)-(lS,3'R)-quinuclidin-3'-yl I-phenyI-l52,3,4-tetrahydro-isoquinoIine-2-carboxylate (Solifenacin)

We Claim:

1. A racemization process for the preparation of 1-phenyl-l, 2,3,4-tetrahydroisoquinoline of a compound of Formula (I), the process comprising:

(a) providing a material comprising a suitable diastereomeric salt of (L/?)-l-phenyl-l,2,3,4-tetrahydroisoquinoline (V);

(b) reacting the material with one or more bases, optionally in the presence of one or more suitable solvents to form (17?)-l-phenyl-l,2,3,4-tetrahydroisoquinoline of a compound of Formula (IB);

(c) reacting the (L/?)-I-phenyl-l,2,3,4-tetrahydroisoquinoline of the compound of Formula (IB) with Halogenating reagents in the presence of suitable base in one or more suitable solvents to obtain a compound of Formula (IV),

Wherein X is chlorine or bromine or iodine etc;

d) hydrolyzing the compound of Formula (IV) in the presence of base or acids in one or more suitable solvents to obtain the 1 -phenyl- 1,2,3,4-tetrahydroisoquinoline racemate of the compound of Formula (I).

2. The process as claimed in claim 1, step (a), wherein the material further comprises (17?)-l-phenyl-l,2,3,4-tetrahydroisoquino!ine of the compound of Formula (IB) such that R:S ratio of the starting mixture is about R:S ratio is about in the range of 10:20 to 60:40, preferably 50:50.

3. A process for the preparation of (^)-2-Chloro-l52,354-tetrahydro-l-phenylisoquinoline compound of formula (IVA):

3. The process as claimed in claim 1, step (b), wherein the suitable base is selected from sodium carbonate, potassium carbonate, sodium bicarbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, ammonia ( or) organic bases like triethyl amine, pyridine, disopropylethyl amine, piperidine, morpholine or mixtures thereof.

5. The process as claimed in claim 1, step (b), wherein the suitable solvent is selected from alcohols, esters, chlorinated solvents, nitriles, hydrocarbons, ketones, aprotic polar, water, or their suitable mixtures.

6. The process as claimed in claim 1, step (c), wherein the suitable Halogenating reagent is selected from N-Chlorosuccinimide, N-Bromosuccinimide, PGs, POCI3, SOCI2, Sulfuryl chloride etc.

7. The process as claimed in claim 1, step (d), wherein the acid is selected inorganic acids such as HC1, H2S04, HBr, HN03 (or) organic acids such as HCOOH, CH3COOH, CH3CH2COOH; lower haloalkyl acid such as CF3COOH, dichloroacetic acid; phosophoric acid, lower alkyl phosphonic acid such as methylphosphonic acid, phenylphosphonic acid, BF3.0Et2 or mixture thereof.

8. A recycling process for the (R) enriched enantiomer of 1-phenyl-1,2,3,4-tetrahydroisoquinoline comprises treatment of diastereomeric salt of (lTJ)-l-phenyl-1,2,3,4-tetrahydroisoquinoline with one or more suitable organic or inorganic base.

9. According to preceding claimed processes are used for the preparation of Solifenacin or a salt thereof.