Field of the invention:
The present invention relates to an improved process for the preparation of trospium chloride. Trospium chloride is chemically known as Azoniaspiro (3a-benzyloyloxynortropane-8,r-pyrrolidine)chloride and is represented by the following compound of formula-1.

Formula-1 Trospium chloride is a quaternary ammonium compound used as an antispasmodic, antimuscarinic agent and is commercially available under the brand name of Sanctura as tablets.
Background of the Invention:
Trospium chloride and its related compounds as well as processes for their preparation have been disclosed in US 3480626. The disclosed process involves the reaction of nortropine benzilate with 1,4-dichlorobutane in acetonitrile at boiling temperature for three days, followed by crystallization of trospium chloride from ethanol-ether. As per this process, the reaction is carried out for very long time i.e., three days which makes the process uneconomic and not viable for the commercial scale. The said process also involves the usage of ether solvent for final crystallization, which in general is not recommendable for commercial scale.
US 4855422 disclosed a process for the preparation of trospium chloride, which involves the reaction of nortropine with 1,4-dichlorobutane in presence of a diethylamine in dimethylformamide when left to stand for 18 days at ambient temperature provides 3 a-hydroxynortropane-8-spiro-r-pyrrolidinium chloride, which is then reacted with benzilic acid imidazole in presence of 4-(dimethylamino)-pyridine in anhydrous acetonitrile at 78°C to provide trospium chloride. The said process involves almost 18 days for

completion of the reaction between nortropine and 1,4-dichlorobutane, which makes the process uneconomic and unsuitable for the commercial scale.
Hence there is a need in the art for an improved process for the preparation of trospium chloride which is commercially viable with minimum process time and avoids all the problems pertaining to the prior art processes.
Brief Description of the Invention:
The first aspect of the present invention is to provide an improved process for the
preparation of (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo[3.2. l]octane-8,r-
pyrrolidinium]chloride compound of formula-4, which comprises of reacting the nortropine compound of formula-2 with 1,4-dihalobutane compound of formula-3 in presence of a suitable organic base in a suitable solvent, followed by recrystallisation from suitable solvents to provide the compound of formula-4.
The second aspect of the present invention is to provide an improved process for the preparation of (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo [3.2.1]octane-8,r-pyrrolidinium]chloride compound of formula-4, which comprises of reacting the nortropine compound of formula-2 with 1,4-dihalobutane compound of formula-3 in presence of a suitable inorganic base in a suitable solvent, followed by recrystallisation from suitable solvents to provide the compound of formula-4,
The third aspect of the present invention is to provide a process for the purification of compound of formula-4 in a suitable solvent to provide the pure compound of formula-4.
The fourth aspect of the present invention is to provide an improved process for
the preparation of trospium chloride compound of formula-1, which comprises of
a) Treating the benzilic acid compound of formula-5 with carbonyldiimidazole in
acetonitrile to provide the benzilic acid imidazole compound of formula-6, which on
in-situ reaction with the compound of formula-4 in presence of a suitable catalyst in
a suitable solvent to provide the trospium chloride compound of formula-1,

b) purifying the trospium chloride compound of formula-1 from suitable solvents or mixtures there of to provide the pure compound of formula-1.
The fifth aspect of the present invention is to provide an improved process for the preparation of trospium chloride compound of formula-1, which comprises of
a) Reacting the compound of formula-4 with benzilic acid compound of formula-5 in presence of DCC and a catalyst in a suitable solvent to provide the trospium chloride compound of formula-1,
b) purifying the trospium chloride compound of formula-1 from suitable solvents or mixtures there of to provide the pure compound of formula-1.
The sixth aspect of the present invention is to provide an improved process for the preparation of trospium chloride compound of formula-1, which comprises of the following steps,
a) Reacting the nortropine compound of formula-2 with 1,4-dihalobutane compoimd of in presence of a suitable organic base in a suitable solvent, followed by recrystalization from a suitable solvent to provide compound of formula-4,
b) Treating the benzilic acid compound of formula-5 with carbonyldiimidazole in acetonitrile to provide the benzilic acid imidazole compound of formula-6, which on in-situ reaction with the compound of formula-4 in presence of a suitable catalyst in a suitable solvent provides the trospium chloride compound of formula-1,
c) Purifying the trospium chloride compound of formula-1 using a suitable solvents or mixtures there of to provide the pure compound of formula-1.
The seventh aspect of the present invention is to provide a process for the purification of trospium chloride compound of formula-1, which comprises of the following steps;
a) Dissolving or suspending the trospium chloride in a suitable solvent at reflux temperature,
b) optionally filtering the reaction mixture,
c) cooling the reaction mixture to 0-5 °C
d) stirring the reaction mixture,

e) filtering the solid, washing it with solvent
f) drying the solid to get the pure compound of formula-1.
Advantageous of the present invention:
• Provides an improved process which avoids the prolonged timecycle
• Provides high pure trospium chloride and its intermediates
• Eco-friendly and commercially viable process
Brief Description of the Drawings:
Figure-1: Illustrates the powder X-ray diffraction pattern of crystalline trospium chloride
prepared as per the process disclosed in US 4855422
Figure-2: Illustrates the IR spectrum of trospium chloride prepared as per the process
disclosed in US 4855422
Figure-3: Illustrates the DSC of trospium chloride prepared as per the process disclosed
in US 4855422
Detailed Description of the Drawings:
The present invention relates to an improved process for the preparation of trospium chloride compound of formula-1, which is represented by the following compound of formula-1

Formula-1 As used herein the term "Inorganic base" refers to alkali metal hydroxide such as lithium hydroxide,sodium hydroxide, potassium hydroxide; alkali metal alkoxide such as sodium methoxide, sodium tertiary butoxide and potassium tertiary butoxide; alkali metal carbonates such as sodium carbonate, potassium carbonate, cesium carbonate; amide bases such as sodium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide,

lithium bis(trimethylsilyl) amide; metal hydrides such as sodium hydride and potassium hydride and the like.
As used herein the term "organic base" refers to dimethylamine, diethylamine, diisopropylamine, dicyclohexylamine, triethylamine, trimethylamine, pyridine, 1,4-Diaza bicyclo[2.2.2]octane (DABCO) and the like.
As used herein the term "polar aprotic solvents" refer to dimethylsulfoxide, dimethylacetamide, dimethyl formamide, tetrahydrofuran and the like; "polar protic solvents" refer to water and the like; "hydrocarbon solvents" refer to toluene, xylene, cyclohexane, hexane, heptane and the like; "ketone solvents" refer to acetone, methyl isobutyl ketone and the like; "esters solvents" refer to ethyl acetate, methyl acetate, n-butyl acetate, isobutyl acetate, sec-butyl acetate, isopropyl acetate and the like; "alcoholic solvents" refer to the methanol, ethanol, isopropanol, 2-butanol, ethylene glycol and the like; "chloro solvents" refer to methylene chloride, ethylene dichloride, carbon tetra chloride, chloroform and the like.
As used herein the term "phase transfer catalyst" refers to the tetra butyl ammonium bromide, tetra propyl ammonium bromide, tributyl benzyl ammonium bromide, tetra octyl ammonium bromide, tetra butyl ammonium iodide, tetra butyl ammonium hydrogen sulfate, benzyl trimethyl ammonium chloride, benzyl triethyl ammonium chloride, tetra butyl ammonium acetate, tetra butyl ammonium iodide, ethyl triphenyl phosphonium bromide and the like.
The first aspect of the present invention provides an improved process for the preparation of (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo [3.2.1]octane-8,r-pyrro lidnium] chloride compound of formla-4, which comprises of the following steps, a) Reacting the nortropine compound of formula-2
HN-


/
OH Formula-2

with 1,4-dihalobutane compound of formula-3
Formula-3 wherein X is halogen,
preferably 1,4-dichlorobutane in presence of a suitable organic base in a suitable solvent selected from polar protic solvents, polar aprotic solvents, alcoholic solvents, nitrile solvents, ketone solvents, chloro solvents, ester solvents or mixtures thereof, at a suitable temperature selected from 45 to 75°C, preferably 50-60°C, for the period of 5 to 25 hours preferably 15-17 hours to provide (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo [3.2.1]octane-8,r-pyrrolidinium]chloride compound of formula-4, b) purifying the compound of formula-4 using a suitable solvent selected from polar protic solvents, alcoholic solvents, nitrile solvents, ketone solvents, chloro solvents, ester solvents or mixtures thereof to provide the pure (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo [3.2.1]octane-8,r-pyrrolidinium]chloride compound of formula-4.

OH Formula-4 As per the prior art processes, the reaction of compound of formula-2 with formula-3 in presence of diethyl amine in dimethyl formamide at ambient temperature for 18 days to provide the compound of formula-4 and also mentioned that increase in temperature results in the formation of by-products. The time cycle for the above process is too high and hence it is not advisable for commercial scale. So in order to reduce the time cycle of the reaction, we have carried out number of reactions by varying process parameters, conditions & solvents in different reaction conditions and finally found that carrying out the reaction at the temperature of around 50 to 70°C led to the completion of reaction with in 15-20 hours without affecting quality and yield and also found that no by-products were formed. Hence the present invention is more advantageous over the prior art process, which reduces the time cycle of the process.

The second aspect of the present invention provides an improved process for the preparation of (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo [3.2.1]octane-8,r-pyrro lidnium] chloride compound of formla-4, which comprises of the following steps, a) Reacting the nortropine compound of formula-2
HN-


/

OH

Fonnula-2 with 1,4-dihalobutane compound of formula-3
Formula-3 Wherein X is halogen,
preferably 1,4-dichlorobutane in presence of a suitable inorganic base in presence or absence of a phase transfer catalyst, in a suitable solvent selected from polar protic solvents, polar aprotic solvents, alcoholic solvents, nitrile solvents, ketone solvents, chloro solvents, ester solvents or mixtures thereof at a suitable temperature selected from 40 to 100°C, preferably 50-80°C for the period of 1 to 3 hours preferably 1.5-2 hours to provide (lR,3R,5S)-3-hydroxyspiro[8-azonibicyclo[3.2.1]octane-8,r-pyrrolidiniumjchloride compound of formula-4,


CI-
r^
V
OH Formula-4 b) purifying the compound of fonnula-4 using a suitable solvent selected from polar protic solvents, alcoholic solvents, nitrile solvents, ketone solvents, chloro solvents, ester solvents or mixtures thereof to provide the pure (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo [3.2.1]octane-8,r-pyrrolidinium]chloride compound of formula-4.

The third aspect of the present invention is to provide a process for the purification of (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo [3.2.1]octane-8,r-pyrrolidinium]chloride compound of formula-4.

OH Formula-4 which comprises of recrystallising the compound of formula-4 from a suitable solvent selected from polar protic solvents, alcoholic solvents, nitrile solvents, ketone solvents, chloro solvents, ester solvents or mixtures there of, at a temperature from 0°C to the reflux temperature of the corresponding solvent used, to provide the pure compound of formula-4.
The fourth aspect of the present invention provides an improved process for the preparation of trospium chloride compound of formula-1, which comprises of the following steps; a) treating the benzilic acid compound of formula-5

Formula-5 with carbonyldiimidazole in presence of dimethylaminopyridine (DMAP), in a suitable solvent selected from polar protic solvents, polar aprotic solvents, alcoholic solvents, nitrile solvents, ketone solvents, chloro solvents, ester solvents or mixtures there of to provide the benzilic acid imidazole compound of formula-6,


Formula-6 which on in-situ reaction with the (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo [3.2.1]octane-8,r-pyrrolidinium]chloride compound of formula-4 provides the trospium chloride compound of formula-1,

0 Formula-1
b) purifying the trospium chloride compound of formula-1 using a suitable solvent
selected from polar protic solvents, alcoholic solvents, nitrile solvents, ketone
solvents, chloro solvents, ester solvents or mixtures there of or mixtures thereof to
provide the pure compound of formula-1.

The fifth aspect of the present invention provides an improved process for the preparation of trospium chloride compound of formula-1, which comprises of the following steps;
c) Reacting the (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo[3.2.1]octane-8,r-
pyrrolidiniumjchloride compound of formula-4,


Nt
CI-

f OH
Formula-4 with benzilic acid compound of formula-5

Formula-5 in presence of N,N'-Dicyclohexylcarbodiimide (DCC) and dimethylaminopyridine (DMAP) in a suitable solvent selected from nitrile solvents, ketone solvents, chloro solvents, ester solvents or mixtures thereof, to provide the trospium chloride compound of formula-1,

O
Formula-1 d) purifying the trospium chloride compound of formula-1 using a suitable solvent selected from polar protic solvents, alcoholic solvents, nitrile solvents, ketone solvents or mixtures there of or mixtures there of to provide the pure compound of formula-1.
The sixth aspect of the present invention provides an improved process for the
preparation of trospium chloride compound of formla-l, which comprises of the
following steps,
a) Reacting the nortropine compound of formula-2
HN-


/

OH

Formula-2 with 1,4-dihalobutane compound of formula-3

X'
Formula-3 wherein X is halogen,
preferably 1,4-dichlorobutane in presence of a suitable organic base selected from dimethylamine, diethylamine, diisopropylamine, dicyclohexylamine, triethylamine, trimethylamine, 1,4-diaza bicyclo[2.2.2]octane (DABCO) and pyridine, preferably diethylamine in a suitable solvent selected from dimethylformamide, dimethyl sulfoxide and tetrahydrofuran preferably dimethylformamide at a suitable temperature from 40 to 100°C, preferably 50-80°C for the period of time from 5 to 25 hours preferably 15-17 hours to provide (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo [3.2.1]octane-8,r-pyrrolidinium]chloride, which on recrystalization from a suitable solvent selected from methylene chloride, chloroform preferably methylene chloride provides the pure (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo [3.2.1]octane-8,r-pyrrolidinium]chloride compound of formula-4,

OH Formula-4 b) treating the benzilic acid compoimd of formula-5


Formula-5 with carbonyldiimidazole in presence of dimethylaminopyridine (DMAP), in a suitable solvent like acetonitrile to provide the benzilic acid imidazole compound of formula-6.

0
Formula-6 which on in-situ reaction with the (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo [3.2.1]octane-8,r-pyrrolidinium]chloride compound of formula-4 provides the trospium chloride compound of formula-1,


Formula-1 c) Purifying the trospium chloride compound of formula-1 using a suitable alcoholic solvents selected from methanol, ethanol, isopropanol, butanol and water or mixtures there of to provide the pure compound of formula-1.
The seventh aspect of the present invention is to provide a process for the purification of trospium chloride compound of formula-!, which comprises of the following steps;
a) Dissolving or suspending the trospium chloride compound of formula-1 in polar protic solvents, alcoholic solvents, nitrile solvents, ketone solvents, chloro solvents, ester solvents or mixtures thereof at reflux temperature,
b) optionally filtering the solution,
c) cooling the reaction mixture to 0-5 °C
d) stirring the reaction mixture,
e) filtering the solid, washing with a suitable solvent,
f) drying the solid to get the pure compound of formula-1.

In the purification process of the present invention, the preferable solvent used is an alcohol, more preferably a mixture of alcohol solvents. The two alcohols can be used in the ratio of 1:99 to 99:1.
The PXRD analysis of trospium chloride was carried out using SIEMENS/D-5000 X-Ray diffractometer using Cu, Ka radiation of wavelength 1.54 A° and continuous scan speed of 0.045°/min. FI-IR spectrum of trospium chloride was recorded on Thermo model Nicolet-380 as KBr pellet. The thermal analysis of trospium chloride was carried out on Waters DSC Q-10 model differential scanning calorimeter.
The related substance of trospium chloride was analyzed by HPLC using the following conditions:
Column: Phenomenex Luna C8, 250 X 4.6 mm, 5 |am; Flow rate: 1.0 ml/min; wavelength: 215 nm; Temperature: 40°C; Load: 20 p,l; and using a mixture of water, acetonitrile, phosphoric acid and triethylamine.
Nortropine is used as a starting material in the present invention has been prepared by the processes known in the art.
The present invention represented by the following scheme:


Carbonyldiimidazole^ Acetonitrile
Base y ^H
Formula-2 ForniuIa-3 FormuIa-4

DMAP Acetonitrile

^ Methanol Yj | HO,
Isopropanol V Q
CI-


The process described in the present invention was demonstrated in examples illustrated below. These examples are provided as illustration only and therefore should not be construed as limitation of the scope of the invention:
Examples:
Example-l: Preparation of (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo
[3.2.1]octane-8,r-pyi'roIidiniuin]chloride compound of formula-4:
Diethylamine (172 grams) and 1,4-dichlorobutane (400 grams) was added to a solution of nortropine (100 grams) in dimethylformamide (1 L) at 25-35°C. The reaction mixture was heated to 50-55°C and stirred for 17 hours. The reaction mixture was cooled to 20-25°C, stirred for 1.5 hours and filtered. Methylene chloride (800 ml) was added to the obtained solid and stirred for 1.5 hour at 40-45°C. The reaction mixture was then cooled to 0-5 °C and stirred for an hour. The solid obtained was filtered, washed with methylene chloride and dried at 80-85°C to get the title compound Yield: 140 grams
Example-2: Preparation of (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo [3.2.1]octane-8,l'-pyi'roIidinium]chloride compound of formuIa-4:
Diethylamine (172 grams) and 1,4-dichlorobutane (400 grams) was added to a solution of nortropine (100 grams) in dimethylformamide (1 L) at 25-35°C. The reaction mixture was heated 50-55°C and stirred for 17 hours. The reaction mixture was cooled and stirred for 1.5 hours. The solid obtained was filtered and washed with dimethyl formamide and dried at 80-85°C to get the title compound. Yield: 144 grams.
Example-3: Purification of (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo [3.2.1]octane-8,r-pyrrolidinium]chloride compound of formuIa-4:
A mixture of methylene chloride (800 ml) and crude compound of formula-4 (144 grams) was heated to 40-45°C and stirred for 1.5 hour at 40-45°C. The reaction mixture was then cooled to 0-5 °C and stirred for an hour. The solid obtained was filtered, washed with methylene chloride and dried at 80-85°C to get the pure title compound. Yield: 138 grams

Exainple-4: Preparation of (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo pj-lloctane-Sjl'-pyrrolidiniumJchloride compound of formula-4:
Potassium carbonate (16.5 grams) and 1,4-dichlorobutane (20 grams) added to a solution of nortropine (5.0 grams) in dimethylformamide (50 ml) at 25-35°C. The reaction mixture was heated to 80°C and stirred for 2.0 hours. The reaction mixture was cooled to 30-35°C and methanol (60 ml) added to the reaction mixture, stirred for 30 minutes and filtered the unwanted solid. Distilled the solvent from the filtrate and methylene chloride (50 ml) was added to the obtained solid and stirred for 90 minutes at 40-45°C and cooled to 0-5°C, stirred for an hour. Filtered the solid and washed with methylene chloride and dried at 80-85°C to get the title compound. Yield: 3.2 grams
£xample-5: Preparation of trospium chloride compound of formuIa-1:
Dimethylaminopyridine (5.6 grams) was added to a solution of benzilic acid (31.5 grams) in acetonitrile (200 ml) and stirred for 15 minutes. Carbonyldiimidazole (27 grams) was added to the reaction mixture under nitrogen atmosphere and stirred for 15 minutes. (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo [3.2.1]octane-8,r-pyrrolidinium] chloride compound of formula-4 (20 grams) was added to the reaction mixture and heated to 80-85°C then stirred for 12 hours. The reaction mixture was cooled to 20-25°C and stirred for 1.5 hours. The solid formed was filtered, washed with acetonitrile and dried at 60-65°C to get the title compound. Yield: 30 grams Purity by HPLC: 99.50%
Example-6: Purification of trospium chloride:
A mixture of trospium chloride (130 grams) in methanol (520 ml) and isopropylalcohol (1.3 L) was heated to reflux temperature, stirred for 30 minutes and the obtained solution was filtered. The filtrate was cooled to 0-5°C and stirred for 1.5 hours at 0-5°C. The solid formed was filtered, washed with isopropyl alcohol and dried at 60-65 °C to get the pure title compound. The PXRD, IR and DSC of the obtained

trospium chloride is similar to the PXRD, IR and DSC shown in figure 1, 2 & 3 respectively. Yield: 112 grams. Purity by HPLC: 99.97%
Example-7: Purification of trospium chloride:
A mixture of trospium chloride (130 grams) in methanol (1.3 L) and isopropylalcohol (520 ml) was heated to reflux temperature, stirred for 30 minutes and the obtained solution was filtered. The filtrate was cooled to 0-5°C and stirred for 1.5 hours at 0-5°C. The solid formed was filtered, washed with isopropyl alcohol and dried at 60-65°C to get the pure title compound. Yield: 108 grams. Purity by HPLC: 99.96%
ExampIe-8: Preparation of trospium chloride compound of formula-1:
Dimethylaminopyridine (5.6 grams) was added to a solution of benzilic acid (31.5 grams) in acetonitrile (200 ml) and stirred for 15 minutes. N,N'-Dicyclohexyl carbodiimide (34 grams) was added to the reaction mixture under nitrogen atmosphere and stirred for 15 minutes. (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo [3.2.1]octane-8,r-pyrrolidinium] chloride compound of formula-4 (20 grams) was added to the reaction mixture and heated to 80-85°C then stirred for 12 hours. The reaction mixture was cooled to 20-25°C and stirred for 1.5 hours. The solid formed was filtered, washed with acetonitrile and dried at 60-65°C to get the title compound. Yield: 28 grams
Example-9: Purification of trospium chloride:
A mixture of trospium chloride (50 grams) methanol (500 ml) and ethyl acetate (200 ml) was heated to reflux temperature, stirred for 30 minutes and the obtained solution was filtered. The filtrate was cooled to 0-5°C and stirred for 1.5 hours at 0-5°C. The solid formed was filtered, washed with isopropyl alcohol and dried at 60-65°C to get the pure title compound. Yield: 43 grams; Purity by HPLC: 99.95%

Example-10: Purification of trospium chloride:
A mixture of trospium chloride (50 grams) methanol (500 ml) and water (200 ml) was heated to reflux temperature, stirred for 30 minutes and the obtained solution was filtered. The filtrate was cooled to 0-5°C and stirred for 1.5 hours at 0-5°C. The solid formed was filtered, washed with isopropyl alcohol and dried at 60-65 °C to get the pure title compound. Yield: 41 grams. Purity by HPLC: 99.92%

We Claim:
1. An improved process for the preparation of trospium chloride compound of formuia-1, which comprises of the following steps,

in presence of a suitable base selected from dimethylamine, diethylamine, diisopropylamine, dicyclohexylamine, triethylamine, trimethylamine, 1,4-Diaza bicyclo[2.2.2]octane (DABCO) and pyridine, in a suitable solvent selected from dimethylformamide, dimethyl sulfoxide and tetrahydrofuran at a suitable temperature from 45 to 75°C, for the period of time from 5 to 25 hours to provide (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo [3.2.1]octane-8,r-pyrrolidinium] chloride, which on recrystallization from a suitable solvent selected from methylene chloride or chloroform provides the pure (lR,3R,5S)-3-hydroxy spiro [8 -azoniabicyclo [3.2.1] octane-8,1' -pyrrolidinium] chloride compound of formula-4,
/ OH
Formula-4 b) treating the benzilic acid compound of formula-5


with carbonyldiimidazole in presence of dimethylaminopyridine (DMAP), in a suitable solvent like acetonitrile to provide the benzilic acid imidazole compound of formula-6,

which on in-situ reaction with (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo [3.2.1]octane-8,r-pyrrolidinium]chloride compound of formula-4 provides the trospium chloride compound of formula-1,

c) Purifying the trospium chloride compound of formula-1 in a suitable alcoholic solvents selected from methanol, ethanol, isopropanol, butanol and water or mixtures there of to provide the pure compound of formula-1.
2. A process for the purification of trospium chloride compound of formula-1, which comprises of the following steps;

a) Dissolving or suspending the trospium chloride in a suitable solvents selected from a polar protic solvents, alcoholic solvents, nitrile solvents, ketone solvents, chloro solvents, ester solvents or mixtures at reflux temperature,
b) optionally filtering the reaction mixtvire,
c) cooling the reaction mixture to 0-5°C,
d) stirring the reaction mixture,
e) filtering the solid, washing with suitable alcoholic solvent,
f) drying the solid to get the pure compound of formula-1.
3. An improved process for the preparation of trospium chloride compound of formla-1, which comprises of the following steps,

in presence of diethylamine in dimethylformamide at the temperature range from 50-60°C for the period of time fi-om 16-18 hours to provide (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo [3.2.1]octane-8,r-pyrrolidinium]chloride, which on recrystalization from methylene chloride provides the pure (1 R,3R,5 S)-3 -hydroxyspiro[8-azoniabicyclo [3.2.1 ]octane-8,1' -pyrrolidinium] chloride compound of formula-4,
f OH Formula-4

b) treating the benzilic acid compound of formula-5

c) purifying the trospium chloride compound of formula-1 from a mixture of
isoproylalcohol and methanol to provide the pure compound of formula-1.
4. A process for the purification of trospium chloride compound of formula-1, which comprises of the following steps;
a) Dissolving the trospium chloride in a mixture of methanol and isopropyl alcohol in the ratio of 1:99 to 99:1 at reflux temperature,
b) filtering the solution,

c) cooling the reaction mixture to 0-5°C,
d) stirring the reaction mixture,
e) filtering the solid, washing with isopropyl alcohol,
f) drying the solid to get the pure compound of formula-1.
5. An improved process for the preparation of (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo [3.2.1]octane-8,r-pyrrolidinium]chloride compound of formula-4,


Nt
CI-
/ OH

Formula-4 which comprise of reacting the nortropine compound of formula-2
HN


y

OH

Formula-2 with 1,4-dihalobutane compound of formula-3
Formula-3 wherein X is halogen,
in presence of a suitable organic base in a suitable solvent selected from polar protic solvents, polar aprotic solvents, alcoholic solvents, nitrile solvents, ketone solvents, chloro solvents, ester solvents or mixtures thereof to provide (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo [3.2.1]octane-8,r-pyrrolidinium] chloride compound of formula-4, characterized in that the reaction carried out at a suitable temperature selected from 45 to 75°C, for the period of time from 10 to 25 hours.
6. The usage of inorganic base in the reaction of nortropine compound of formula-2 with 1,4-dihalobutane compound of formula-3 in a suitable solvent to provide the

(lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo[3.2.1]octane-8,r-pyrrolidinium]chloride compound of formula-4.
7. An improved process for the preparation of (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo [3.2.1]octane-8,r-pyrrolidinium]chloride compound of formula-4,

o.

CI-

f OH
Formula-4 which comprise of reacting the nortropine compound of formula-2
HN


/

OH

Formula-2 with 1,4-dihalobutane compound of formula-3
Formula-3 Wherein X is halogen,
in presence of a suitable inorganic base in a suitable solvent selected firom polar protic solvents, polar aprotic solvents, alcoholic solvents, nitrile solvents, ketone solvents, chloro solvents, ester solvents or mixtures thereof to provide (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo [3.2.1]octane-8,r-pyrrolidinium] chloride compound of formula-4.
8. A process for the purification of (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo [3.2.1]octane-8,r-pyrrolidinium]chloride compound of formula-4 which comprises of recrystallisation from a suitable solvent selected from polar protic solvents, alcoholic solvents, nitrile solvents, ketone solvents, chloro solvents, ester solvents or

mixtures there of, at a temperature selected from 0°C to the reflux temperature of the corresponding solvent used, to provide the pure compound of formula-4.
9. A process for the purification of (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo
[3.2.1]octane-8,r-pyrrolidinium]chloride compound of formula-4 which comprises
of
a) suspending the compound of formula-4 in methylene chloride at reflux
temperature,
b) stirring the reaction mixture at reflux,
c) cooling the reaction mixture to 0-5°C,
d) filtering the solid, washing with methylene chloride and drying to get the pure compound of fonnula-4.
10. An improved process for the preparation of trospium chloride compound of formula-
1, which comprises of reacting the (lR,3R,5S)-3-hydroxyspiro[8-azoniabicyclo
[3.2.1]octane-8,r-pyrrolidinium]chloride compound of formula-4 with benzilic acid
compound of formula-5 in presence of N,N'-Dicyclohexylcarbodiimide (DCC) and
dimethylaminopyridine (DMAP) in a suitable solvent selected from alcoholic
solvents, nitrile solvents, ketone solvents, chloro solvents, ester solvents or mixtures
there of to provide the trospium chloride compound of formula-1.