FIELD OF THE INVENTION:

The present invention relates to an improved process for preparation of Rotigotine or an acid addition sail thereof. The present invention also relates to process for the preparation of crystalline Rotigotine hydrochloride and crystalline Rotigotine base. The present invention further relates to crystalline (-)-5-hydroxy-N-n-propyl-2-aminotetralin, a key intermediate used in the preparation of Rotigotine.

BACK GROUND OF THE INVENTION:

Rotigotine is a new non-ergolinic dopamine agonist and is marketed under the brand name of "NEUPRO". Neupro is indicated for the treatment of the signs and symptoms of early-stage idiopathic Parkinson's disease. It is formulated as 10 cm^, 2Qcn:i^, 30 cm^ and 40 cm^ transdermal patches containing respectively 4.5 mg, 9.0 mg, 13.5 mg and 18.0 mg of Rotigotine and designed to release respectively 2 mg, 4 mg, 6 mg, and 8 mg of Rotigotine per 24 hours. Rotigotine, (6S)-6-(prQpyl-(2-thiophen-2-ylethyl)amino)tetralin-1-ol has the following structure

U.S. Pat No. 4,885,308 discloses process for obtaining the two optical isomers of Rotigotine by resolving the racemic 5-methoxy-2(N-propylamino)tetralin to its enantiomers, then converting each enantiomer to (+) or (-) Rotigotine, using the process as disclosed in U.S. Pat No. 4,564628.

U.S. Pat No. 6,372,920 discloses a process for the preparation of Rotigotine hydrochloride, which involves the condensation of (-)-5-hydroxy-N-n-propyl-2-aminotetralin with 2-(2-thienyl)ethanol toluenesulfonate in the presence of alkali metal carbonate or alkali metal bicarbonate (in c 1.9 fold molar excess with respect the amine starting material) in xylene yields (-)-5-hydroxy-2-[N-n- propyl-N2-(2-thienyl)cthylamino]tetralin. The stepwise process is as shown in the scheme-li given below:

PCT Application No, WO 2008/146284 discloses a process for the preparation of crystalline Rotigotine base of polymorph Form I by treating Rotigotine hydrochloride in a mixture water and water immiscible organic solvent in presence of base, organic and aqueous layer is separated, combined organic layer is concentrated under reduced pressure to get residue. Water is added to the residue and removed water by distillation to give reside, which is treated with diethyl ether and removed the solvent followed by addition n-hexane to give Rotigotine crystalline base.

None of the prior art process disclose the commercial process for the preparation of Rotigotine, Moreover, prior art process involves the use of Pt02 and BBrs for the preparation of Rotigotine which are hazardous and not viable for the industrial scale. The present invention overcomes all the problems associated with the prior art and is commercially viable and industrially scalable.

OBJECT OF THE INVENTION:

The main object of the present invention is to provide an improved process for preparation of Rotigotine or its acid addition salt.

Another object of the present invention is to provide crystalline Rotigotine hydrochloride.

Yet another object of the present invention is to provide crystalline Rotigotine base and process for the preparation of the same.

Yet another object of the present invention is to provide crystalline (-)-5-hydroxy-N-n-propyl-2-aminotetralin, a key intermediate used in the preparation of Rotigotine,

SUMMARY OF THE INVENTION

The main aspect of the present invention is to provide an improved process for preparation of Rotigotine or its acid addition salt, which comprising the steps of: (a) reacting 5-methoxy-2-tetralone with n-propyl amine in presence of an acid in a solvent to give Schiff base of formula (la), *hich in turn is reacted in-situ with a reducing agent to give compound of formula (I); (b) treating compound of formula (I) with optically active acid to give optically active diastereomeric mixture of compound of formula (II), (c) optionally purifying compound of formula (11} in a solvent to give pure compound of formula (II); (d) demethylating of compound of formula (II) in presence of an acid and catalyst to get compound of formula (III) and (e) reacting compound of formula (III) with 2-(2-thienyl)ethanol toluene sulfonate in the presence of dipotassium hydrogen phosphate followed by reacting with hydrochloric acid in-situ to give Rotigotine hydrochloride.

The stepwise process is shown in the scheme-Ill given below:

Another aspect of the present invention is to provide crystalline Rotigotine hydrochloride having the PXRD pattern shown in figure-4.

Yet another aspect of the present invention is to provide crystalline Rotigotine base having the PXRD pattern shown in figure-5; the process for the preparation of Rotigotine base which comprising the steps: (a) dissolving the Rotigotine acid addition salt in a mixture of water and water immiscible organic solvent in presence of base, (b) separating the water immiscible organic solvent, optionally treating with carbon, (c) cooling the solution of step b and (d) isolating crystalline Rotigotine base.

Yet another aspect of the present invention is to provide crystalline{-)-5-hydroxy-N-n-propyl-2-aminotetralin having the PXRD pattern shown in figure-3

BRIEF DESCRIPTION OF THE DRAWINGS:

FIG. 1 is a representative X-ray diffraction pattern of 5-methoxy-N-n-propyl-2-aminotetrafin.
FIG, 2 is a representative X-ray diffraction pattern of (-)-5-methoxy-N-n-propyl-2-aminotetraNn di-benzoyl tartaric acid.
FIG. 3 is a representative X-ray diffraction pattern of (-)-5-hydroxy-N-n-propyl-2-aminotetralin.
FIG, 4 is a representative X-ray diffraction pattern of Rotigotine hydrochloride.
FIG, 5 is a representative X-ray diffraction pattern of Rotigotine free base.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to an improved process for preparation of Rotigotine or an acid addition salt thereof. The present invention also relates to process for the preparation of crystalline Rotigotine hydrochloride and crystalline Rotigotine base. The present invention further relates to a crystalline (-)'5-hydroxy-N-n-propyl-2-aminotetralin, a key intermediate used in the preparation of Rotigotine,

The main aspect of the present invention is to provide an improved process for preparation of Rotigotine or its acid addition salt, which comprising the steps of:

a) reacting 5-methoxy-2-tetralone with n-propyl amine in presence of an acid in a suitable solvent to give schiff base of formula (la), which in turn is reacted in-situ with a reducing agent to give compound of formula (1)

b) eating compound of formula (I) with optically active acid to give optically active diastereomeric mixture of compound of formula {II)

c) optionally purifying compound o^ formula (11) in a solventto give pure compound of formula (II)

d) demethylatrng of compound of formula (II) in presence of an acid and catalyst to get formula (III)

e) reacting compound of formula (III) with 2-{2-thienyl)ethanol toluene sulfonate in the presence of dipotassium hydrogen phosphate followed by reacting with hydrochloric acid in-situ to give Rotigotine hydrochloride.

According to the present invention, 5-methyl-2-tetralone is reacted with n-propyl amine in a solvent in the presence of catalytic amount of an acid to give schiff base followed by reduction of the schiff base in situ in the presence of a reducing agent to give 5-methoxy-N-n-propyl-2-aminotetralin. The organic solvent is selected from toluene, xylene, acetonitrile, dimethylformamide, tetrahydrofuran, dioxane, diethyl ether or mixtures thereof. The reducing agent is selected from sodium borohydride, sodium cyanoborohydride or platinum oxide preferably sodium borohydride and more preferably sodium borohydride in acetic acid (STAB).

Another embodiment of the present invention wherein, the racemic 5-methoxy-N-n-propyl-2-aminotetralin is treated with an optically active acid and optionally purifying diastereomeric mixture thus formed. Optically active acid is selected from enantiomerically pure dibenzoyi tartaric acid, tartaric acid, mandelic acid, camphor sulphonic acid, or diparatolyl tartaric acid, preferably (-)-dibenzoyl tartaric acid. Purification of the diastereomeric mixture is carried out in presence of a solvent selected from water, ethyl acetate, acetone, methylisobutyl ketone, acetonitrile, methanol, ethanol, isopropanol or mixtures thereof, preferably mixture of acetone, ethylacetate and water.

Yet another embodiment of the present invention, demethylation is carried out in a solvent in the presence of an acid and a catalyst. The acid is selected from hydrobromic acid and the catalyst is selected from hydrogen iodide, hydrogen chloride, sodium iodide, potassium iodide or lithium iodide, preferably sodium iodide- Solvent used for demethylation reaction is selected from the group comprising of chlorinated hydrocarbons, aromatic or aliphatic hydrocarbons, ketones, esters or nitriles such as methylene dichloride, chloroform, acetonitrile, cyclohexane, tetrahydrofuran, xylene, N-methylpyrrolidone, ethyl acetate, acetone, methylisobutyl ketone or toluene, preferably ethylacetate.

Another embodiment of the present invention wherein, the condensation of (-) 5-hydrDxy-N-n-propyl-2-aminotetralin with 2-(2-thienyl)ethanol toluenesulfonate is carried out in the presence of dipotassium hydrogen phosphate in a solvent to give Rotigotine, followed by in-situ salt formation with hydrogen chtoride in a solvent.

Solvent used for condensation reaction is selected from the group comprising of ketones, aliphatic hydrocarbons, esters or nitriles such as acetonitrile, cyclohexane, tetrahydrofuran, dioxane, xylene, N-methytpyrrolidone, ethyl acetate, acetone, methylethylketone, methylisobutyl ketone or toluene, preferably methyl isobutyl ketone.

The solvent used in hydrochloride salt formation is selected from the group of ketones, aliphatic hydrocarbons, esters or nitriles such as acetonitrile, cyclohexane, tetrahydrofuran, dioxane, xylene, N-methylpyrrolidone, ethyl acetate, acetone, methylethylketone, methylisobutyl ketone or toluene, preferably acetone.

Another embodiment of the present invention, the crystalline (-)-5-hydroxy-N-n-propyl-2-aminotetralin is characterized by X-ray powder diffraction pattern with characteristic peaks expressed in degree 26 values at 9.77, 13.73, 14,27, 14.85, 15.25, 15,77, 16.50, 17.53, 17,99, 18.83, 19.68, 21.57, 21.84, 22,13, 22.68, 23.30, 23.52, 23.95, 24.33, 24.89, 25.44, 26.05, 27,35, 28,79, 29-82, 30.20 and 31,74 ± 0.2 as shown in Fig. 3.

Yet another embodiment of the present invention is to provide crystalline Rotigotine hydrochloride is characterized by X-ray powder diffraction pattern with characteristic peaks expressed in degree 29 values at 7.09, 9.54, 9.73, 9,98, 13.19, 13.76, 14,10, 14,79, 16,30, 17.72, 17.99, 19,49, 19.78, 20.14, 21.36, 22.21, 22,42, 22.90, 23.50, 25.84, 26,36, 27,78, 29.48 and 31.08 ± 0,2,

Yet another embodiment of the present invention, the crystalline Rotigotine hydrochloride is characterized by X-ray powder diffraction pattern as shown in Fig. 4.

Another embodiment of the present invention, the crystalline Rotigotine base is characterized by X-ray powder diffraction pattern as shown in Fig. 5 with characteristic peaks expressed in degree 29 values at 10.76, 12.60, 13.12, 14.60, 15,24, 15.60, 16.61, 17.00, 19.68, 20.17, 21,88, 22,53, 24,21, 24.46, 25.05, 25.38, 26.20, 27.28, 27.79 and 29.44 ± 0,2 .

Another embodiment of the present invention provides process for the preparation of Rotigotine base which comprising the steps: a} dissolving the Rotigotine acid addition salt in a mixture of water and water immiscible organic solvent in presence of base b) separating the water immiscible organic solvent, optionally treating with carbon c) cooling the solution from step b and d) isolating crystalline Rotigotine base.

Another embodiment of the present invention, Rotigotine acid addition salt is suspended in a mixture of water and water immiscible organic solvent in the presence of base. Rotigotine acid salt is selected from fiydrochloric acid or hydrobromic acid, water immiscible organic solvent is selected from aliphatic hydrocarbons such as cyclohexane, methylcyclohexane, toluene, preferably methylcyclohexane.

The base used for converting acid addition salt of Rotigotine to Rotigotine free base is selected from sodium bicarbonate, potassium bicarbonate preferably sodium bicarbonate.
The aqueous sodium bicarbonate or potassium bicarbonate solution is added to the above suspension and heated the resulting solution to get clear solution, then separated the organic layer. The organic layer is optionally treated with carbon and filtered, clear filtrate is subjected to cooling to get crystalline Rotigotine base, which is filtered and washed with solvent to give pure crystalline Rotigotine base.

The following non-limiting examples illustrate specific embodiments of the present invention. They should not construe it as limiting the scope of present invention in any way.

Example-1: 5-niethoxy-N-n-propyl-2-aminotetralin.
To the mixture of 5-methoxy-2-tetralone {lOOg) and toluene (500ml) was added acetic acid (102.2g) at 25-30''C. n-propylamine (40,25g) was added to this mixture for about 30-40 min and cooled to 15°C for about 10-15 min. Sodium borohydride (28g) was added portion wise to the reaction mixture and stirred for about 20 hrs. Filtered the solid and washed with toluene (200ml), To the filtrate aqueous hydrochloric acid (100ml) was added at 25-30°C, cooled the reaction mixture to lO-IS'C for about 30 min and maintained at the same temperature for about 60 min. Filtered the obtained solid and washed the solid with acetone (300ml). Dried the solid under vacuum to obtain125-130 g of the title compound characterized by X-ray powder diffraction pattern as shown in Figure 1 with peaks at 6.92, 11.40, 12.30, 13.87, 14,63, 15.06, 17.61, 18.74, 23.34, 23.67, 24,45, 24,75, 25.60, 27.44, 27.99, 29.26, 31,69, 34.08, 35.00, 37,48, 39.92 and 45.41 ±0.29 values.

Example-2: (-)-5-methoxy-N-n-propyl-2-aminotetralin di-benzoyi tartaric acid.
To the mixture of DM water {200ml) and sodium bicarbonate (49g) was added 5-methoxy-N-n-propyl-2-aminotetralin (100g), ethylacetate (600ml) at 25-30°C and heated the mixture to 70-75°C for about 30-45 min. Stirred the reaction mixture at the same temperature for about 60 min and cooled to 30-40''C for about 30 min. Separated the organic layer and heated to 65-75°C for about 30-45 min. Di-benzyl tartaric acid solution in ethylacetate {116g in 150 ml) was added to the reaction mixture at 65-75°C for about 90-120 min and cooled the reaction mixture to 25-35''C for about 120-150 min. Filtered the obtained solid and washed with ethylacetate (150 ml). Acetone (120ml), ethylacetate {900ml) was added to the wet compound thus obtained at 25-30°C and heated the mixture to 72-78''C. DM water (600mi) was added to the reaction mixture, refluxed for about 30 min at 72-78''C and cooled the reaction mixture to 25-35''C for about 120 min. Filtered the solid and dried the solid under vacuum to yield 45-55 g of the title compound characterized by X-ray powder diffraction pattern as shown in Figure 2 with peaks at 6.45, 7.16, 14.42, 16.09, 17,39, 18.20, 19.43, 20.46, 21.59, 23.26, 26.15, 26.60 and 27.66 ± 0.29 values.

Example-3: (-)5-hydroxy-N-n-propyl-2-aminotetralin:
Sodium iodide (25.95g) was added to {-)-5-methoxy-N-n-propyl-2-aminotetralin di-benzoyI tartaric acid (lOOg) at 25-35''C for about 30-40 min. Aqueous Hydrobromic acid (200ml) was added to the mixture and heated to 110-120°C for about 60-90 min. Cooled the reaction mixture to 60-70°C for about 60 min and ethylacetate {200ml) was added. Stirred the reaction mixture for about 30 min at 60-70''C and cooled to 25-30°C for about 60 min. Filtered the obtained solid and washed with ethylacetate (100ml). The wet material thus obtained was added to a mixture of water (400ml), sodium bicarbonate {29.0g) and ethylacetate {300ml). Stirred the mixture at 25-30°C for about 120 min. Filtered the solid and washed the solid with ettiylacetate (lOOml). Dried the solid under vacuum to get 25-30 g of the title compound characterized by X-ray powder diffraction pattern as shown in Figure 3 with peaks at 9.77, 13.73, 14.27, 14.85, 15.25, 15.77, 16.50, 17.53, 17.99, 18.83, 19.68, 21.57, 21,84, 22,13, 22,68, 23,30, 23,52, 23,95, 24,33, 24.89, 25.44, 26.05, 27.35, 28.79, 29.82, 30.20 and 31.74 ± 0.26 values.

Example-4: 2-(2-thienyl)ethanol toluenesulfonate:
Mixture of toluene (400ml), thiophene ethanol (lOOg), p-toluene sulphonyl chloride (163,2g) and dimethyl amino pyridine (5g) were cooled to 10-15''C and triethylamine (130g) was added to the reaction mass for about 60-90 min. Stirred the reaction mass for about 240 min and DM water {600ml) was added to the reaction mass. Stirred the reaction mass for about 30 min and separated the organic layer. Water {600ml) washed the organic layer and concentrated under vacuum, DM water (400ml) was added to the residue thus obtained at 25-30''C, heated the mixture to 50-55''C for 30 min and maintained at the same temperature for about 45 min. Separated the organic layer and concentrated under vacuum to yield 200-210 g of the title compound.

Example-5: (-) 5-hydroxy-2-(N-n-propyl-N-2-thienylethyl)-aminotBtralin hydrochroride (Rotigotine hydrochloride):
To the mixture of methyl isobutyl ketone (1500ml), {-)-5-hydroxy-N-n-propyl-2-aminotetralin (lOOg) and 2-(2-thienyl)ethanol toluenesuifonate {412,7g) was added dipotassium hydrogen phosphate (59.0g) at 25-30''C and heated to 100-120°C for about 24-30 hrs. Cooled the reaction mass to 25-30''C, filtered the inorganic salts and washed the salts with methyl isobutyl ketone (200ml), Washed the combined methyl isobutyl ketone layer with DM water (2 X 200ml), Concentrated the methyl isobutyl ketone layer under vacuum. Acetone {1000ml), aqueous HCI were added to the residue and stirred for about 3 hrs. Filtered the obtained solid and washed with acetone {100ml).To the wet compound thus obtained was added acetone (500ml) and heated to get clear solution for about 2 hrs. Cooled the reaction mixture to 25-30X for about 1 hr, filtered the solid obtained and washed with acetone (50ml). n-propanol (400ml) was added to the wet solid, heated the reaction mass to 80-90°C. Activated carbon (8g) was added to the reaction mass at 80-90''C and maintained at the same temperature for about 30 min. Filtered the carbon, washed the carbon bed with n-propanol (4Qml) and cooled the reaction mass to ZS-SCC for about 3- 4hrs. Filtered the solid and washed with n-propanol (50ml). Dried the solid under vacuum to get 75-80g of the title compound characterized by X-ray powder diffraction pattern as shown in Figure 4 with peaks at 7.09, 9.54, 9.73, 9.98, 13.19, 13.76. 14.10, 14.79, 16,30, 17.72, 17.99, 19.49, 19.78, 20.14, 21.36, 22.21, 22.42, 22.90, 23.50, 25.84, 26.36, 27.78, 29.48 and 31.08 ±0,26 values.

Example-6: {-)5-hydroxy-2-(N-n-propyl-N-2-thlenylethyl)-amlnotetralin (Rotigotine):
To the mixture of methyl isobutyl ketone (1500ml), (-)-5-hydroxy-N-n-propyl-2-aminotetralin (lOOg) and 2-(2-thienyl)ethanol toluenesuifonate (412.7g) was added didipotassium hydrogen phosphate (92,5g) and DM water (12-18ml) at 25-30''C and heated to 110-120''C for about 24 hrs. Cooled the reaction mass to 25-30''C, filtered the inorganic salts and washed the salts with methyl isobutyl ketone (200ml). To the filtrate thus obtained was added aqu HCI {64,85g) and concentrated under vacuum. Acetone (500mt) was added the residue and stirred the mixture for about 90 min. Filtered the solid and washed the solid with acetone (100ml). Acetone (500ml) was added to the wet material thus obtained at 25-30''C, heated to 55-58°C and maintained at the same temperature for about 60 min. Cooled the reaction mixture to 25-30°C and stirred at the same temperature for about 60 min. Filtered the solid and washed with acetone (100ml). DM water (500ml) was added to sodium bicarbonate (61.5g) at 25-30''C, stiired for about 60 min and methyl cyclohexane {500ml) was added. The wet material was added to this mixture and heated to 50-gCC for about 30 min. Cooled the reaction mixture to 60-65ºC and separated the aqueous layer. Activated carbon in methyl cyclohexane (7g in 100ml) was added to the reaction mass, filtered the carbon and washed the carbon bed with methyl cyclohexane (100ml). Cooled the filtrate to 25-30''C and maintained at the same temperature for about 240 min. Filtered the solid and washed the solid with methyl cyclohexane {100ml). Dried the solid under vacuum to get 75-lOOgof the title compound characterized by X-ray powder diffraction pattern as shown in Figures with peaks at 10.76, 12.60, 13.12. 14.60, 15.24, 15.60, 16.61, 17.00, 19.68, 20.17, 21.88, 22.53, 24.21, 24,46, 25-05, 25,38, 26.20, 27.28, 27.79 and 29.44 ± 0,26 values.

We claims;

1. Improved process for the preparation of Rotigotine hydrochloride comprising the steps of: a) reacting 5-methoxy-2-tetratone with n-propyl amine in presence of an acid in a solvent to give schiff base of formula (la), which in turn is reacted in-situ with a reducing agent to give compound of formula (I)


b) treating compound of formula (I) with optically active acid to give optically active diastereomeric mixture of compound of formula (II)

c) optionally purifying of compound of formula cli) in a solvent to give pure compound of formula (II)

d) demethylating compound of formula (II) in presence of acid and catalyst to get compound of formula (Ill)

e) reacting compound of formula (Ill) with 2-(2-thienyl)ethanol toluene sulfonate in the presence of dipotassium hydrogen phosphate followed by reacting with hydrochloric acid in-situ to give Rotigotine hydrochloride.

2. Improved process for the preparation of Rotigotine base comprising the steps of:

a) reacting 5-methoxy-2-tetralone with n-propyl amine in presence of an acid in a solvent to give schiff base of formula (Ia), which in turn is reacted in-situ with a reducing agent to give compound of formula (I)

b) treating compound of formula (I) with optically active acid to give optically active diastereomeric mixture of compound of formula (II)

c) optionally purifying compound of formula (II) in a solvent to give pure compound of formula (II)

d) demethylating compound of formula (II) in compound formula (Ill)

e) reacting compound of formula (Ill) with 2-(2-thienyl)ethanol toluene sulfonate in the presence of dipotassium hydrogen phosphate followed by reacting with an acid in- situ to give Rotigotine acid addition salt

f) dissolving the acid addition salt obtained in step e), in a mixture of water and water
immiscible organic solvent in presence of base,

g) separating the water immiscible organic solvent, optionally treating with carbon,

h) cooling the solution from step g and

i) isolating crystalline Rotigotine base.

3. A process according to claim 1&2, wherein solvent used for schiff base is selected from toluene, xylene, acetonitrile, dimethylfornnamide, tetrahydrofuran, dioxane, diethyl ether or mixtures thereof.

4. A process according to claim 1S.2, wherein the reducing agent is selected from sodium borohydride, sodium cyanoborohydride or platinum oxide preferably sodium borohydride and more preferably sodium borohydride in acetic acid (STAB).

5. A process according to claim 1&2, wherein the optically active acid used in step b) is selected from dibenzoyi tartaric acid, tartaric acid, mandelic acid, camphor sulphonic acid, or diparatolyl tartaric acid.

6. A process according to claim 1&2, wtierein optionally crystallization of formula (11) from a solvent is selected from water, ethyl acetate, acetone, methylisobutyl ketone, acetonitrile, methanol, ethanol. isopropanol or mixtures thereof.

7. A process according to claim 1&2, wherein the acid used in demethylation reaction is selected from hydrogen bromide.

8. A process according to claim 1&2, wherein catalyst used in demethylation reaction is selected from sodium iodide, potassium iodide or lithium iodide.

9. A process according to claim 2 of step (e), wherein acid is selected from hydrogen chloride, hydrogen bromide or hydrogen sulphate.

10. A process according to claim 2 of step (f), wherein water immiscble organic solvent group is selected from aliphatic hydrocarbons such as cyclohexane, methylcyclohexane, toluene.

11. Crystalline Rotigotine hydrochloride.

12. A Crystalline Rotigotine hydrochloride is characterized by PXRD pattern having 2 theta values at 9.54, 9,73, 17.72 and 17.99 ± 0.2.

13. A crystalline Rotigotine hydrochloride according to claim 10, wherein the crystalline hydrochloride PXRD pattern is shown in Fig; 4

14. Process for the preparation of crystalline Rotigotine base which comprising the steps of:

a) dissolving the Rotigotine acid addition salt in a mixture of water and water immiscible organic solvent in presence of base,

b) separating the water immiscible organic solvent, optionally treating with carbon,

c) cooling the solution from step b and

d) isolating crystalline Rotigotine base.

15. A process according to claim 14 of step (a), wherein Rotigotine acid addition salt is selected from hydrogen chloride, hydrogen bromide or hydrogen sulphate,

16. A process according to clam 14 of step (a), wherein water immiscible organic solvent group is selected from aliphatic hydrocarbons such as cyclohexane, methylcyclohexane, toluene.

17. A process according to claim 14 of step (a), wherein base is selected from sodium bicarbonate or potassium bicarbonate.

18. A crystalline Rotigotine base according to claim 14, wherein the crystalline Rotigotine base PXRD pattern is shown in Fig; 5.

19. Crystalline (-)-5-hydroxy-N-n-propyl-2-am!notetralin characterized by PXRD pattern shown in figure; 3

20. Improved process for the preparation of Rotigotine or acid addition salt by using Crystalline (-)-5-hydroxv-N-n-propyl-2-aminotetraltn.