FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
The Patent Rules, 2003
COMPLETE SPECIFICATION
[Section 10, and Rule 13]
IMPROVED PROCESS FOR THE PREPARATION OF SOLIFENACIN SUCCINATE
Applicant
Name; Torrent Pharmaceuticals Limited
Nationality; Indian
Address: Torrent House, Off Ashram Road,
Near Dinesh Hall,
Ahmadabad 380 009.
Gujarat, India
The following specification particularly describes the nature of the invention and the manner in which it is to be performed:

FIELD OF THE INVENTION
The present invention relates to an improved, environmental friendly, green process for the preparation of solifenacin succinate.This invention also relates to a process for the recovery and reusability of 3(R)-quinuclidinol and 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline.
BACKGROUND OF THE INVENTION
1(S), 3(R)-1-azabicyclo[2.2.2]-oct-3-yl-3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarbo-xylate succinate known as solifenacin under the International Non-Proprietary Name is marketed as a succinate sa}t. Solifenacin is indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. Solifenacin base can be represented by (1), and was disclosed in U.S. Pat. No. 6,017,927 (the '927 patent).

The '927 patent discloses two preparation methods for the preparation of solifenacin. The first preparation method as depicted in scheme-l, includes condensation of ethyl 1(S)-phenyl-1,2,3,4-tetrahydro-2-isoquinolinecarboxylate (2; R = Et) with 3(R)-quinuclidinol (3). The second preparation method as depicted in scheme-ll, includes condensation of 1(S)-phenyl-1,2,3,4-tetrahydroisoquino!ine (4) with 3(R)-quinuclidinyl chloroformate (5).
It has been observed that the condensation between ethyl 1(S)-phenyl-1,2,3,4-tetrahydro-2-isoquinolinecarboxylate (2; R = Et) with 3{R)-quinuclidinol (3) requires very strong base like sodium hydride. Use of sodium hydride at commercial scale

requires water free facility, it react violently when comes in contact with air or moisture, it is explosive in nature and hence not advisable to use at commercial scale. The another drawback of the process is, even after the use of a very strong base like sodium hydride the reaction takes 48 hours to complete.
It has also been observed that during the condensation reaction, 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline (4) is generated in the reac tion mixture as an impurity in amount of 5 to15%. As this impurity is difficult to remove, the product i.e. solifenacin base (1) isolated from the reaction mixture also contains 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline (4) as an impurity. It results in the extra purification which increase the cost.

For the above mentioned reasons, the condensation reaction is not industrially feasible. Hence, there remains a need in the art to modify the reaction in such a way that it becomes industrially feasible.

It has been observed that use of catalytic quantity of environmental friendly green alkali hydroxide base like sodium hydroxide, potassium hydroxide and the like during condensation reaction of alkyl 1(S)-phenyl-1,2,3,4-tetrahydro-2-isoquinoline-carboxylate (2) with 3(R)-quinuclidinol (3) increase the purity and yield of the final product, is less hazardous and easy to handle than sodium hydride.
It has also been observed that addition of acetic anhydride or acetyl chloride into the reaction mixture of alkyl 1(S)-phenyl-1,2,3,4-tetrahydro-2-isoquinolinecarboxylate (2) and 3(R)-quinuclidinol (3) results in a more pure solifenacin base (1). Effective removal of the impurity 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline (4) results in recovery of 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline (4) which results in reduction of the cost.
It has also been observed that simple and environment friendly recovery process for costly 3(R)-quinuclidinol (3) have direct impact on the cost. 3(R)-quinuclidinol (3) is recovered up to 60% of actual use in the present process.
The commercial manufacturing process of Solifenacin Succinate has the following disadvantages:
(1) The commercial process is not an environmentally benign or "green" approach.
(2) The process has high environmental factor (E factor).
(3) The process use explosive and hazardous base like sodium hydride.
(4) No recovery and reuse of the key byproducts like 3(R)-quinuclidinol (3) and 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline (4).
The present invention is an environmental-friendly green process. In order to develop environmental & echo friendly technology following efforts has been done:
(1) Reduced amount of waste is generated per kg of the product by recovering 3(R)-quinuclidinol (3) and 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline (4).
(2) Recovered intermediates are reused in the process which helps to develop cost effective process for the API.

(3) No hazardous waste is generated in overall process.
(4) Environmental factor (E factor) of present improved green process is less than-25 where as in general commercial manufacturing process, E factor in pharmaceutical field is found to be in between 25 to100.
(5) The process is cost effective and commercially viable.
SUMMARY OF THE INVENTION
The present invention relates to an improved environmental friendly green process for the preparation of solifenacin succinate.This invention also relates to a process for the recovery and reusability of 3(R)-quinuclidinol and 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline.
In one embodiment, the specification discloses a process for the preparation of solifenacin base or salts thereof (1) without using phase transfer catalyst comprises following steps:
a) reacting 3(R)-quinuclidinol (3) with a base in a suitable solvent;
b) adding alkyl 1(S)-phenyl-1,2,3,4-tetrahydro-2-isoquinoline- carboxylate (2) to the reaction mixture of step a);
c) refluxing the reaction mixture of step b) for sufficient time to complete the reaction;
d) recovering 3(R)-quinuclidinol (3);
e) adding acetic anhydride or acetyl chloride;
f) stirring the reaction mixture;
g) isolating solifenacin base (1) or salts thereof.
In another embodiment, the specification discloses a process for recovery of 3(R)-quinuclidinol comprises following steps:
a) reacting 3(R)-quinuclidinol (3) with a base in a suitable solvent;
b) adding alkyl 1(S)-phenyl-1,2,3,4-tetrahydro-2-isoquinoline- carboxylate (2) to the reaction mixture of step a);

c) refluxing the reaction mixture of step b) for sufficient time to complete the reaction;
d) recovering 3(R)-quinuclidinol (3).
In yet another embodiment, the specification discloses a process for the recovery of 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline (4) and its pharmaceutically acceptable salts, which comprises of the following steps:
a) providing a solution of 1(S)-2-acetyl-1-phenyl-1,2,3,4-tetrahydroisoquinoline (6) in a solvent
b) adding acid to the reaction mass of step a);
c) refluxing the reaction mass of step b) for sufficient time to complete the reaction;
d) recovering 1(S)-phenyM,2,3,4-tetrahydroisoquinoline (4),
In yet another embodiment, the specification discloses a process for reuse of 3(R)-quinuclidinol (3) and 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline (4) for the preparation of solifenacin and its phamnaceutically acceptable salts.
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to an improved environmental friendly green process for the preparation of solifenacin succinate.This invention also relates to a process for the recovery and reusability of 3(R)-quinuclidinol and 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline.
In one embodiment, the specification discloses a process for the preparation of solifenacin base or salts thereof (1) without using phase transfer catalyst comprises following steps:
a) reacting 3(R)-quinuclidinol (3) with a base in a suitable solvent;
b) adding alkyl 1(S)-phenyl-1,2,3,4-tetrahydro-2-isoquinoline- carboxylate (2) to the reaction mixture of step a);

c) refluxing the reaction mixture of step b) for sufficient time to complete the reaction;
d) recovering 3(R)-quinuclidinol (3);
e) adding acetic anhydride or acetyl chloride;
f) stirring the reaction mixture;
g) isolating solifenacin base or salts thereof (1).
In another embodiment, the specification discloses a process for recovery of 3(R)-quinuciidinol comprises following steps:
a) reacting 3(R)-quinuclidinol (3) with a base in a suitable solvent;
b) adding alkyl 1{S)-phenyl-1,2,3,4-tetrahydro-2-isoquinoline- carboxylate (2) to the reaction mixture of step a);
c) refluxing the reaction mixture of step b) for sufficient time to complete the reaction;
d) recovering 3(R)-quinuclidinol (3).
The solvent for this reaction may be selected from a group of aromatic and aliphatic hydrocarbon solvent like benzene, toluene, xylene, cyclohexane; ether solvent like tetrahydrofuran, dioxane, dimethoxyethane; dimethylformamide; dimethylsulphoxide; dimethylacetamide; sulfolane and mixture thereof.
The base is selected from a metal such as sodium, potassium and the like; metal hydroxide, metal alkoxide and mixture thereof. The metal hydroxide base is selected from sodium hydroxide, potassium hydroxide, lithium hydroxide, magnesium hydroxide, calcium hydroxide, and mixture thereof. The most preferred metal hydroxide is sodium hydroxide. The metal alkoxide base is selected from sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, sodium tert-butoxide, potassium tert-butoxide and mixture thereof. The most preferred metal alkoxide base is sodium methoxide. The quantity of base that is to be added to the reaction is found to be 1.0 to 3.0 equivalent compared to alkyl 1 (S)-phenyM,2,3,4-tetrahydro-2-isoquinoline-carboxylate{2).

It has been observed that the condensation reaction between alkyl 1(S)-phenyl-1,2,3,4-tetrahydro-2-isoquinolinecarboxylate (2) with 3(R)-quinuclidinol (3) generates 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline (4) in the reaction mixture as an impurity in amount of 5 to 15%. It has been observed that this impurity can not be removed by normal acid-base treatment as expected. Hence the product i.e. solifenacin base (1) isolated from the reaction mixture also contains 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline (4) as impurity in an amount of 5 to 15%.
The reaction between alkyl 1(S)-phenyl-1,2,3,4-tetrahydro-2-isoquinolinecarboxylate (2) and 3(R)-quinuclidinol (3) is carried out as described above. The process comprises reacting 3(R)-quinuclidinol (3) with a base in a suitable solvent and adding alkyl 1(S)-phenyl-1,2,3,4-tetrahydro-2-isoquinoline- carboxylate (2) to the reaction mixture. The reaction mixture is further heated up to the reflux temperature for sufficient time to complete the reaction. After the reaction is over, the reaction mixture is cooled to room temperature and stirred.
In one embodiment, 3(R)-quinuclidinol recovered as a precipitated solid, can be separated by filtration. After filtration, the precipitated solid is washed with toluene and suck dried to obtain recovered 3 (R)-quinuclidinol (3).
After recovering, the filtrate is washed with water and basified with sodium carbonate. Acetic anhydride or acetyl chloride is added to the above filtarte and stirred for 1 hour in order to convert 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline (4) into its N-Acetyl derivative (6).


The reaction mixture is quenched with water and acidified to pH 1-2 by addition of 1N HCI. The aqueous layer is separated from organic layer containing 1(S)-2-acetyl-1-phenyl-1,2,3,4-tetrahydroisoquinoline (6) as byproduct and aqueous layer is basified to pH 8.5 by the addition of 20 % sodium carbonate solution. The aqueous layer is further extracted with organic solvent like ethyl acetate to form organic layer.The organic layer i.e. ethyl acetate layer containing solifenacin base (1) is separated and washed with water and distilled to obtain pure solifenacin base (1).
Table 1 shows that when the condensation reaction between alkyl 1(S)-phenyl-1,2,3,4-tetrahydro-2-isoquinolinecarboxylate (2) with 3(R)-quinuclidinol (3) is worked up without the treatment of acetic anhydride or acetyl chloride, the isolated product, solifenacin base (1) contains more than 5.0% of 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline (4) as impurity. But when the above mentioned condensation reaction is treated with acetic anhydride or acetyl chloride as described above, the said impurity level in the isolated solifenacin base (1) is less than 0.5 %. The solifenacin base (1) may be oily residue or solid residue. The solifenacin base (1) is oily residue.
Table 1

Condition Impurity during reaction Impurity in solifenacin
monitoring by HPLC (%) base by HPLC (%)
Without addition 7.60% 7.94%
of acetylating
agent
Addition of 6.26% Not detected
acetylating agent
The obtained acetyl derivative (6) is hydrolyzed to get recovered 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline (4).


In yet another embodiment, the specification discloses a process for the recovery of 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline (4) and its pharmaceutically acceptable salts, which comprises of the following steps:
a) providing a solution of 1(S)-2-acetyl-1-phenyl-1,2,3,4-tetrahydroisoquinoline (6) in a solvent;
b) adding acid to the reaction mass of step a);
c) refluxing the reaction mass of step b) for sufficient time to complete the reaction;
d) recovering 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline (4),
A solution of 1(S)-2-acetyl-1-phenyl-1,2,3,4-tetrahydroisoquinoline (6) as byproduct is obtained by layer separation after the reaction of alkyl 1(S)-phenyl-1,2,3,4-tetrahydro-2-isoquinoline- carboxylate (2) and 3(R)-quinuclidinol (3) in presence of acetic anhydride or acetyl chloride. The solution of 1(S)-2-acetyl-1-phenyl-1,2,3,4-tetrahydroisoquinoline (6) is obtained from the reaction of alkyl 1(S)-phenyl-1, 2,3,4-tetrahydro-2-isoquinoline-carboxylate (2) and 3(R)-quinuclidinol (3) in presence of acetic anhydride or acetyl chloride in a solvent, followed by treating with aqueous acid to form layers i.e. organic and aqueous layer. The solution of 1(S)-2-acetyl-1-phenyl-1, 2, 3,4-tetrahydroisoquinoline (6) is obtained by separating organic layer containing 1(S)-2-acetyl-1-phenyl-1,2,3,4-tetrahydroisoquinoline (6) as byproduct from aqueous layer.
An acid is added to the reaction mass and the reaction mass is heated to reflux for sufficient time to complete the reaction. The solvent may be removed by distillation with or without vacuum at elevated temperature. Further ethyl acetate is added to the

reaction mass. The aqueous layer is separated and is basified with suitable base. The aqueous solution is then extracted with ethyl acetate and the organic layer is distilled out completely under vacuum to obtain 1 (S)-phenyl-1,2,3,4-tetrahydroisoquinoline (4).
The solvent for this reaction may be selected from alcoholic solvents such as methanol, ethanol, isopropanol, n-butanol and the like; ethers such as diethyl ether, dimethyl ether, diisopropyl ether, tetrahydrofuran and the like; hydrocarbon solvents such as toluene, xylene and the like; polar aprotic solvents such as dimethylformamide, dimethylsulphoxide and the like; chlorinated solvents such as dichloromethane, chloroform, carbon tetrachloride, chlorobenzene and the like; and mixtures of such solvents and water in various proportions.
The acid may be selected from hydrochloric acid, hydrobromic acid, sulfuric acid and the like. Suitably, aqueous solutions containing about 5% to 50%, or about 10% to 20%, (w/v) of the corresponding acid can be used.
Suitable temperature for conducting the reaction, range from about 10°C to about 120°C,depend on the choice of solvent. The reaction temperature is 30 -35°C.
In yet another embodiment, the specification discloses a process for reuse of 3(R)-quinuclidinol (3) and 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline (4) for the preparation of solifenacin and its pharmaceutically acceptable salts.
In still another embodiment, the solifenacin base (1) prepared by a method as described above can be further converted to any acid addition salt by any method known in the art. Preferably, solifenacin base (1) prepared by a method as described above is converted to solifenacin succinate by any method known in the art.
The starting materials, 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline (4) and 3(R)-quinuclidinol (3) are prepared as per the processes known in the art.

ADVANTAGES OF THE INVENTION:
The process of the present invention can be prepared by a simple operation, is easily recoverable and reusable after the completion of reaction, and is extremely advantageous from the viewpoint of "green chemistry (sustainable chemistry)".
The present invention is an environmental-friendly green process. In order to develop environmental & echo friendly technology following efforts has been done:
(1) Reduced amount of waste is generated per kg of the product by recovering 3(R)-quinuclidinol (3) and 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline (4).
(2) Recovered intermediates are reused in the process which helps to develop cost effective process for the API.

(3) No hazardous waste is generated in overall process.
(4) Environmental factor (E factor) of present improved green process is less than 25 where as in general commercial manufacturing process, E factor in pharmaceutical field is found to be in between 25 to100.
(5) The process is cost effective and commercially viable.
The method of preparation of solifenacin base (1) and solifenacin succinate as described herein may be illustrated by the following examples which are not to be construed as limiting the scope of the invention:
EXAMPLE 1
Preparation of ethyl 1(S)-phenyl-1,2,3,4-tetrahydro-2-isoquinolinecarboxy-
late (2)
100 gm 1(S)-phenyl-1, 2, 3, 4-tetrahydroisoquinoline (4) and 900 ml toluene were charged in round bottom flask under nitrogen atmosphere at 27±3°C. 45.64 gm anhydrous sodium carbonate powder was added to the reaction mass and slowly the solution of 56.84 gm ethylchloroformate and 100 ml toluene was added to the reaction mass over the period of 45 minutes. The reaction mass was stirred for

2.0 hours. 1000 ml water was added to the reaction mass and the organic layer and aqueous layer were separated. The organic layer was washed twice with 1000 ml of water. The pH of second water wash was maintained 7±0.5. The organic layer was distilled under vacuum at 45-50°C till volume of organic layer becomes 200 ml.
EXAMPLE 2
Preparation of solifenacin base (1)
181.46 gm of 3(R)-quinuclidinol (3) and 938 ml of toluene were charged in a round bottom flask equipped with Dean-Stark apparatus. 24.76 gm sodium hydroxide powder was added to the reaction mass. The reaction mass was heated at 114±3°C for 3.0 hours and water was removed azeotropically. The organic layer of ethyl 1(S)-phenyl-1,2,3,4-tetrahydro-2-isoquinolinecarboxylate (2) of example 1 (134 gm in 268 ml toluene) was charged to the reaction mass and maintained at 114±3°C. After the completion of the reaction, the reaction mass was cooled to 20±3°C and stirred for 4.0 hours. The solid was precipitated and filtered. The solid contain unreacted 3(R)-quinuclidinol (3) which was washed with 268 ml of toluene and suck dried. The solid was further dried at 45-50°C for 15-20 hours and 3(R)-quinuclidinoi (3) recovered up to 60%.
The filtrate was washed twice with 1340 ml water and dried with 33.5 gm sodium sulphate. 20.38 gm sodium carbonate and 10.06 gm acetyl chloride were added to the filtrate and stirred for 1.0 hour. 1340 ml water was added to the reaction mass and pH was adjusted to 2±0.5 by aqueous hydrochloric acid. The aqueous layer was separated from organic layer. The organic layer containing 1 (S)-2-acetyl-1 -phenyl-1,2,3,4-tetrahydroisoquinoline (6) was used in example 4 for the recovery of 1(S)-phenyl-1, 2, 3, 4-tetrahydroisoquinoline (4). The aqueous layer was further extracted with 1340 ml ethyl acetate. The pH was adjusted to 8.5±0.5 by 536 ml 20% aqueous sodium carbonate solution and the aqueous and organic layers were separated. The aqueous layer was again extracted with 670 ml ethyl acetate

and the aqueous and organic layers were separated. The above two organic layers were combined, washed with water and distilled under vacuum to get oily residue. 134 ml acetone was added to the oily residue and the solvent was distilled under vacuum to get oily residue of solifenacin base (1). Purity: 99.73%
EXAMPLE 3
Preparation of solifenacin succinate
To a round bottom flask 31 gm solifenacin base was dissolved in 844.4 ml acetone at 27±3°C. 14.74 gm charcoal was added to the above solution and stirred for 30 minutes. The suspension was filtered through hyflow. 52.85 gm of succinic acid was added to the above filtrate and the reaction mass was heated at reflux temperature (58±3°C). The reaction mass was cooled to 27±3°C and was stirred for 1.0 hour. The reaction mass was further cooled to 3±2°C and was stirred for 2.0 hours. The reaction mass was filtered, washed with 73.70 ml acetone and suck dried. The obtained wet cake was charged in to the round bottom flask and 4422 ml acetone was charged to it. The reaction mass was heated to reflux (58±3°C) to obtain the clear solution. The acetone was distilled atmospherically from the reaction mass. The reaction mass was cooled to 3±2°C and was stirred for 2.0 hours. The precipitated solid was filtered, washed with acetone and dried under vacuum at 50 °C. Purity: 99.95% Yield: 83.33%
EXAMPLE 4
Recovery of 1(S)-phenyl-1, 2, 3, 4-tetrahydroisoquinoline (4)
5.0 gm N-acetyl 1(S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline (obtained from example 2) and 100 ml 1:1 mixture of water and methanol were charged in round bottom flask. 50 ml 15% aqueous hydrochloric acid solution was added to the above

reaction mass and was heated up to the reflux temperature. Methanol was distilled at 30-35°C under vacuum. 50 ml ethyl acetate was added to the above reaction mass and was stirred for 10 minutes. The aqueous layer was separated and was basified with sodium carbonate. The reaction mass was extracted with ethyl acetate. The organic layer was washed with 20 ml water and was distilled out completely under vacuum at 25-30°C.

We claim:
1. A process for the preparation of solifenacin base or salt thereof (1) without using
phase transfer catalyst comprising the steps of;
h) reacting 3(R)-quinuclidinol (3) with a base in a suitable solvent;
i) adding alkyl 1(S)-phenyl-1,2,3,4-tetrahydro-2-isoquinoline- carboxylate (2) to the
reaction mixture of step a);
j) refluxing the reaction mixture of step b) for sufficient time to complete the
reaction;
k) recovering 3(R)-quinuclidinol (3);
I) adding acetic anhydride or acetyl chloride;
m) stirring the reaction mixture;
n) isolating solifenacin base or salt thereof (1).
2. A process for the recovery of 3(R)-quinuclidinol comprising the steps of;
a) reacting 3(R)-quinuclidinol (3) with a base in a suitable solvent;
b) adding alkyl 1(S)-phenyl-1,2,3,4-tetrahydro-2-isoquinoline- carboxylate (2) to the
reaction mixture of step a);
c) refluxing the reaction mixture of step b) for sufficient time to complete the
reaction;
d) recovering 3(R)-quinuclidinol (3).
3. The process according to claim 1 and 2, wherein the suitable solvent is selected from the group comprising of aromatic and aliphatic hydrocarbon, preferably benzene, toluene, xylene, cyclohexane; ethers, preferably tetrahydrofuran, dioxane, dimethoxyethane; dimethylformamide; dimethylsulphoxide; dimethylacetamide; sulfolane and mixture thereof.
4. The process according to claim 1 and 2, wherein the base is selected from the group comprising of metal, preferably sodium, potassium and the like; metal hydroxide, preferably sodium hydroxide, potassium hydroxide, lithium hydroxide, magnesium hydroxide, calcium hydroxide, more preferably sodium hydroxide; metal

alkoxide, preferably sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, sodium tert-butoxide, potassium tert-butoxide, more preferably sodium methoxide and mixture thereof.
5. The process according to claim 1 and 2, wherein the recovery of 3{R)-quinuciidinol comprises precipitation, filtration, washing, drying and the like.
6. A process for the recovery of 1{S)-phenyl-1,2,3,4-tetrahydroisoquinoline (4) and its pharmaceutically acceptable salts comprising the steps of;

e) providing a solution of 1(S)-2-acetyl-1-phenyl-1,2,3,4-tetrahydroisoquinoline (6) in a solvent,
f) adding acid to the reaction mass of step a);
g) refluxing the reaction mass of step b) for sufficient time to complete the reaction;
h) recovering 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline (4).
7. The process according to claim 6, wherein the solvent is selected from the group comprising of alcoholic solvents preferably methanol, ethanol, isopropanol, n-butanol and the like; ethers preferably diethyl ether, dimethyl ether, diisopropyl ether, tetrahydrofuran and the like; hydrocarbon solvents preferably toluene, xylene and the like; polar aprotic solvents preferably dimethylformamide, dimethylsulphoxide and the like; chlorinated solvents preferably dichloromethane, chloroform, carbon tetrachloride, chlorobenzene and the like; and mixtures of such solvents and water in various proportions.
8. The process according to claim 6, wherein the acid is selected from hydrochloric acid, hydrobromic acid, sulfuric acid and the like, preferably aqueous solutions containing about 5% to 50%, or about 10% to 20%, (w/v) of the corresponding acid.
9. The process according to according to claim 6, wherein step (c), reaction mixture is heated to a reflux temperature, preferably in the range of between about 10°C -120°C, more preferably 30 -35°C.

10. The process of claim 2 and 6, further comprises conversion of recovered 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline (4) and its pharmaceutically acceptable salts or recovered 3(R)-quinuclidinol (3) for the preparation of solifenacin or salts thereof.