Field of the Invention:

The present invention relates to an improved process for the preparation of N-[2-(7-methoxy-l-naphthyI)ethyl]acetamide, represented by the following structural formula-1. Further, the present invention also relates to novel process for the purification of intermediate compounds of said compound of formula-1.

Formula-1
N-[2-(7-methoxy-l-naphthyl)ethyl]acetamide (herein after referred as agomelatine) is an antidepressant developed by the pharmaceutical company Servier and marketed under the trade names Valdoxan, Melitor and Thymanax. Agomelatine was approved by EMEA in Europe on 20 February 2009 under the brand name Valdoxan.

Background of the Invention:
N-[2-(7-methoxy-l-naphthyl)ethyl]acetamide and process for its preparation was first disclosed in US 5225442. The disclosed process involves eight steps, starting from 7-methoxy-1-tetralone. The said process involves the reaction of 7-methoxy-l-tetralone with ethyl bromo acetate, followed by aromatization and saponification to yield the corresponding acid, which is then converted into acetamide and subsequently dehydrated to yield (7-methoxy-l-naphthyl)acetonitrile, this being followed by reduction, and then condensation with acetyl chloride. As the said process involves more number of steps, thus makes the process more expensive and time-consuming. Hence there is a need to provide a process with less number of steps.

Brief description of the Invention:
The first aspect of the present invention is to provide an improved process for the preparation of N-[2-(7-methoxy-l-naphthyl)ethyl]acetamide compound of formula-1, comprising of:

a) Dehydrogenating the 2-(l-hydroxy-7-methoxy-l,2,3,4-tetrahydronaphthalen-l-yl) acetonitrile compound of formula-2 with DDQ in toluene to provide 2-(l-hydroxy-7-methoxy-1,2-dihydronaphthalen-1 -yl)acetonitrile compound of formula-3,

b) treating the compound of formula-3 in-situ with inorganic acid in toluene to provide 2-(7-methoxynaphthalen-l-yl)acetonitrile compound of formula-4,

c) optionally purifying the compound of formula-4 from methanol to provide pure compound of formula-4,

d) reducing the compound of formula-4 with Raney nickel in presence of methanolic ammonia in water under hydrogen pressure to provide 2-(7-methoxynaphthalen-l-yl)ethanamine compound of formula-5,

e) treating the compound of formula-5 in-situ with ethylacetate-hydrochloric acid in ethyl acetate provides 2-(7-methoxynaphthalen-l-yl)ethanamine hydrochloride compound of formula-6,

f) optionally purifying the compound of formula-6 from a mixture of ethyl acetate and methanol to provide pure compound of formula-6,

g) acetylating the compound of formula-6 with acetyl chloride in presence of potassium carbonate in a mixture of water and ethyl acetate to provide compound of formula-1,

h) optionally purifying the compound of formula-1 by dissolving in dimethylformamide and followed by adding water to it to provide pure compound of formula-1.

The second aspect of the present invention is to provide one pot process for the preparation of 2-(7-methoxynaphthalen-l-yl)acetonitrile compound of formula-4, comprising of:

a) Dehydrogenating the 2-(l-hydroxy-7-methoxy-l,2,3,4-tetrahydronaphthalen-l-yl) acetonitrile compound of formula-2 with DDQ in toluene to provide 2-(l-hydroxy-7-methoxy-1,2-dihydronaphthalen-1 -yl)acetonitrile compound of formula-3,

b) treating the compound of formula-3 in-situ with inorganic acid in toluene to provide 2-(7-methoxynaphthalen-l-yl)acetonitrile compound of formula-4,

c) optionally, purifying the compound of formula-4 from methanol to provide pure compound of formula-4.

The third aspect of the present invention is to provide one pot process for the preparation of 2-(7-methoxynaphthalen-l-yl)ethanamine hydrochloride compound of formula-6, comprising of:

a) Reducing the 2-(7-methoxynaphthalen-l-yl)acetonitrile compound of formula-4 with Raney nickel in presence of methanolic ammonia in water under hydrogen pressure to provide 2-(7-methoxynaphthalen-l-yl)ethanamine compound of formula-5,

b) treating the compound of formula-5 in-situ with ethylacetate-hydrochloric acid in ethyl acetate provides 2-(7-methoxynaphthalen-l-yl)ethanamine hydrochloride compound of formula-6,

c) optionally, purifying the compound of formula-6 from a mixture of ethyl acetate and methanol to provide pure compound of formula-6.

The fourth aspect of the present invention is to provide a process for the purification of 2-(7-methoxynaphthalen-l-yl)acetonitrile compound of formula-4, comprising of:

a) Dissolving the 2-(7-methoxynaphthalen-l-yl)acetonitrile compound of formula-4 in methanol at 40-50°C,

b) cooling the reaction mixture, and

c) filtering the solid and then dried to get pure compound of formula-4.

The fifth aspect of the present invention is to provide a process for the purification of 2-(7-methoxynaphthalen-l-yl)ethanamine hydrochloride compound of formula-6, comprising of:

a) Adding the 2-(7-methoxynaphthalen-l-yl)ethanamine hydrochloride compound of formula-6 to a mixture of ethyl acetate and methanol,

b) heating the reaction mixture to 50-55°C,

c) stirring the reaction mixture,

d) cooling the reaction mixture, and

e) filtering the solid and then dried to get pure compound of formula-6.

The sixth aspect of the present invention is to provide a process for the preparation of crystalline form-I of N-[2-(7-methoxy-l-naphthyl)ethyl] acetamide compound of formula-1, comprising of:

a) Dissolving the N-[2-(7-methoxy-l-naphthyl)ethyl]acetamide compound of formula-1 in dimethylformamide by heating to 40-45°C,

b) cooling the reaction mixture,

c) adding water to the reaction mixture,

d) stirring the reaction mixture,

e) filtering the solid and then dried to get crystalline form-I of compound of formula-1.
Advantages of the present invention:

• Usage of commercially available and cheaper reagents and solvents like hydrochloric acid and water.

• Provides highly pure intermediates which in-turn results in the formation of highly pure N-[2-(7-methoxy-1 -naphthyl)ethyl]acetamide compound of formula-1.

• The usage of water as a solvent in the conversion of compound of formula-3 to compound of formula-4 reduces the cost.

• Provides eco-friendly and cost-effective process.

Brief description of drawings:

Figure-1: Illustrates the PXRD pattern of crystalline form-I of JV-[2-(7-methoxy-l-naphthyl)ethyl] acetamide compound of formula-1.

Figure-2: Illustrates the PXRD patt ern of 2-(7-methoxynaphthalen-l-yl)ethanamine hydrochloride compound of formula-6.

Detailed description of the Invention:
The term "suitable inorganic acid" herein the present invention is selected from hydrochloric, hydrobromic acid, sulfuric acid, phosphoric acid and the like.

The present invention relates to an improved process for the preparation of N-[2-(7-methoxy-l-naphthyl)ethyl]acetamide compound of formula-1 and also relates to the novel process for the purification of its intermediate compounds.

The first aspect of the present invention is to provide an improved process for the preparation of N-[2-(7-methoxy-l-naphthyl)ethyl]acetamide compound of formula-1, comprising of:

a) Dehydrogenating the 2-(l-hydroxy-7-methoxy-l,2,3,4-tetrahydronaphthalen-l-yl)
acetonitrile compound of formula-2

Formula-2 with DDQ in toluene to provide 2-(l-hydroxy-7-methoxy-l,2-dihydronaphthalen-l-yl)acetonitrile compound of formula-3,

Formula-3

b) treating the compound of formula-3 in-situ with inorganic acid in toluene to provide
2-(7-methoxynaphthalen-l-yl)acetonitrile compound of formula-4,

Formula-4
c) optionally, purifying the compound of formula-4 from methanol to provide pure compound of formula-4,
d) reducing the compound of formula-4 with Raney nickel in presence of methanolic ammonia in water under hydrogen pressure to provide 2-(7-methoxynaphthalen-l-yl)ethanamine compound of formula-5,

Formula-5 e) treating the compound of formula-5 in-situ with ethylacetate-hydrochloric acid in ethyl acetate provides 2-(7-methoxynaphthalen-l-yl)ethanamine hydrochloride compound of formula-6,
Formula-6

f) optionally purifying the compound of formula-6 from a mixture of ethyl acetate and methanol to provide pure compound of formula-6,

g) acetylating the compound of formula-6 with acetyl chloride in presence of potassium carbonate in a mixture of water and ethyl acetate to provide compound of formula-1,

h) optionally, purifying the compound of formula-1 by dissolving in dimethylformamide
and followed by adding water to it to provide pure compound of formula-1. Wherein,
in step-a) DDQ used in the range of 0.5 to 5 molar equivalents to 1 mole of compound of
formula-2; and toluene is used in the range of 20 to 60 volumes to per lg of
compound of formula-2, in step-b) inorganic acid used is selected from hydrochloric acid, hydrobromic acid and sulfuric acid, preferably hydrochloric acid, in step-c) the methanol used in the range of 1 to 10 volumes per lg of compound of formula-2, in step-d) the methanolic ammonia used in the range of 1 to 20 volumes per 1 g of compound of formula-4, in step-f) the ratio of methanol to ethyl acetate is between 9.5:0.5 and 8:2. in the step-f) above aspect the compound of formula-6 can be also purified using a
mixture of toluene and methanol.

The 2-( 1 -hydroxy-7-methoxy-1,2,3,4-tetrahydronaphthalen-1 -yl)acetonitrile compound of formula-2 of the present invention is commercially available or can be prepared from by the known methods or from the method disclosed in WO2012046253.

The usage of p-toluene sulfonic acid for the dehydration of 2-(l-hydroxy-7-methoxy-l,2-dihydronaphthalen-l-yl)acetonitrile compound of formula-3 was disclosed in Synthetic communication, 2001, 31 (4), 621-629. The same process was conducted in the laboratory and observed the formation of unknown impurity at 1.67 RRT with content of 0.5% by HPLC in the preparation of 2-(7-methoxynaphthalen-l-yl)acetonitrile compound of formula-4. The present inventors also carried out the dehydration of compound of formula-3 with hydrochloric acid and surprisingly found that, the unknown impurity which is formed at 1.67 RRT was reduced to the level of 0.03% by HPLC which meets the ICH guide lines. Moreover, the usage of p-toluene sulfonic acid requires the heating of the reaction mixture contents to complete the reaction. Whereas, the usage of hydrochloric acid avoids the heating of the reaction mixture contents thereby advisable for the dehydration of compound of formula-3.

Synthetic communication, 2001, 31(4), 621-629 was disclosed the process for preparation of 2-(7-methoxynaphthalen-l-yl)acetonitrile compound of formula-4 from 2-(l-hydroxy-7-methoxy-l,2,3,4-tetrahydronaphthalen-l-yl)acetonitrile compound of formula-2 by dehydrogenating with DDQ in dichloromethane, followed by dehydrating the compound with p-toluene sulfonic acid in dichloromethane. The same process was conducted in the laboratory using dichloromethane as a solvent and followed by purification with methanol results in the formation of compound of formula-4 with purity 95%. The same process was also conducted using toluene as a solvent, followed by purification with methanol produced the compound of formula-4 with purity greater than 99.56%. The present inventors also observed the formation of unknown impurity at 1.67 RRT at a level of 0.5% by HPLC. The same impurity was reduced to the level of 0.05% or to not detected level when the reaction was conducted in toluene, hence the present process is advantageous over the prior art process.

The second aspect of the present invention is to provide one pot process for the preparation of 2-(7-methoxynaphthalen-l-yl)acetonitrile compound of formula-4, comprising of:

a) Dehydrogenating the 2-(l-hydroxy-7-methoxy-1,2,3,4-tetrahydronaphthalen-l-yl)acetonitrile compound of formula-2 with DDQ in toluene to provide 2-(l-hydroxy-7-methoxy-1,2-dihydronaphthalen-1 -yl)acetonitrile compound of formula-3,

b) treating the compound of formula-3 in-situ with inorganic acid in toluene to provide 2-(7-methoxynaphthalen-l-yi)acetonitrile compound of formula-4,

c) optionally, purifying the compound of formula-4 from methanol to provide pure compound of formula-4.

The prior reported processes involves the dehydrogenation of compound of formula-2 to provide compound of formula-3 and the obtained compound was isolated and then dehydrated to give compound of formula-4. The isolation of compound of formula-3 may reduce the yield of final compound. Whereas, the present inventors are not isolating the compound of formula-3 which in-situ dehydrated with inorganic acid to provide compound of formula-4 which avoids the reduction of the yield of final compound.
The third aspect of the present invention is to provide one pot process for the preparation of 2-(7-methoxynaphthalen-l-yl)ethanamine hydrochloride compound of formula-6, comprising of:

a) Reducing 2-(7-methoxynaphthalen-l-yl)acetonitrile compound of formula-4 with Raney nickel in presence of methanolic ammonia in water to provide 2-(7-methoxynaphthalen-l-yl)ethanamine compound of formula-5,

b) treating the compound of formula-5 in-situ with ethylacetate-hydrochloric acid in ethyl acetate to provide 2-(7-methoxynaphthalen-l-yl)ethanamine hydrochloride compound of formula-6,

c) optionally, purifying the compound of formula-6 from a mixture of ethyl acetate and methanol to provide pure compound of formula-6.

The fourth aspect of the present invention is to provide a process for the purification of 2-(7-methoxynaphthalen-l-yl)acetonitrile compound of formula-4, comprising of:

a) Dissolving the 2-(7-methoxynaphthalen-1-yl)acetonitrile compound of formula-4 in methanol at 40-50°C,

b) cooling the reaction mixture,

c) filtering the solid and then dried to get pure compound of formula-4.

The usage of toluene for purification of compound of formula-4 as per the reported process resulted in the compound with less yield as the compound is more soluble in toluene, hence is not advisable for purification of compound of formula-4. The present inventors replaced the toluene with methanol, as it is resulted in the formation of compound of formula-4 with enhanced yields.

The purity of compound of formula-4 also increased from 97.46 % to 99.53% by HPLC after purification from methanol. The following are the details of impurities mentioned in terms of their RRT in HPLC along with its % area, which are observed in the compound of formula-4 before and after purification with methanol.

The fifth aspect of the present invention is to provide a process for the purification of 2-(7-methoxynaphthalen-l-yl)ethanamine hydrochloride compound of formula-6, comprising of:

a) Adding the compound of formula-6 to a mixture of ethyl acetate and methanol,
b) heating the reaction mixture to 50-55°C,
c) stirring the reaction mixture,
d) cooling the reaction mixture,
e) filtering the solid and then dried to get pure compound of formula-6.

The 2-(7-methoxynaphthalen-l-yl)ethanamine hydrochloride compound of formula-6 which is obtained as per the process disclosed in Journal of medicinal chemistry, 1994, 37 (20), 3231-3239 i.e. after recrystallization from ethanol resulted in the product with lower yields (i.e. 88%). Whereas, the present invention provides a process for the purification of compound of formula-6 from a mixture of ethyl acetate-ethanol which results in the formation of product with high yield (i.e. 100%) and high purity (99.76% by HPLC). The impurity which is observed at 1.11 RRT with the content of 0.16 % was reduced to 0.06 % when purified from a mixture of ethyl acetate and methanol.

The sixth aspect of the present invention is to provide a process for the preparation of crystalline form-I of iV-[2-(7-methoxy-l-naphthyl)ethyl] acetamide compound of formula-1, comprising of:

a) Dissolving N-[2-(7-methoxy-l-naphthyl)ethyl]acetamide compound of formula-1 in dimethylformamide by heating to 40-45°C,

b) cooling the reaction mixture,

c) adding water to the reaction mixture,

d) stirring the reaction mixture,

e) filtering the solid and then dried to get crystalline form-I of compound of formula-1.

In the step-b) of the above aspect, the reaction mixture was cooled to -45 to 10°C, preferably -35 to -30°C.

The impurities observed in the preparation of Agomelatine of the present invention are shown in the following table with their structures along with their % area as follows:

Table-1:
All the prior reported processes for the preparation of crystalline form-I of N-[2-{l-methoxy-l-naphthyl)ethyl]acetamide compound of formula-1 leads to unstable crystalline form, as it is converting into crystalline form-II. Whereas, the crystalline form-I of compound of formula-1 of the present invention is stable.

PXRD of N-[2-(7-methoxy-l-naphthyl)ethyl]acetamide was carried out using BRUKER/AXS X-Ray diffractometer using Cu Ka radiation of wavelength 1.5406 A° and continuous scan speed of 0.03°/min.
N-[2-(7-methoxy-l-naphthyl)ethyl]acetamide compound of formula-1 obtained by the present invention was analyzed by HPLC under the following conditions: Apparatus: A liquid chromatograph equipped with variable wavelength UV detector; Column: Zorbax SB C18, 250 x 4.6mm, 5μm or equivalent; Flow rate: 1.0 ml/min; Wavelength: 210 nm; Column temperature: 60°C; Injection volume: 5 μL; Run time: 58 min; Diluent: methanol:water (50:50)v/v; Mobile phase-A: Buffer; Mobile phase-B: Acetonitrile: methanol: water (80:10:10) v/v.

2-(7-methoxynaphthalen-l-yl)acetonitrile compound of formula-4 of the present invention was analyzed by HPLC under the following conditions:
Apparatus: A liquid chromatograph equipped with variable wavelength UV detector; Column: Zorbax SB-CN, 100 x 4.6mm, 3.5μm or equivalent; Flow rate: 0.8 ml/min; Wavelength: 220 nm; Column temperature: 15°C; Injection volume: 5 uL; Run time: 50 min; Diluent: methanol:water (50:50)v/v; Elution: gradient; Mobile phase-A: Buffer; Mobile phase-B: Acetonitrile: Buffer (70:30) v/v.

2-(7-methoxynaphthalen-l-yl)ethanamine hydrochloride compound of formula-6 of the present invention was analyzed by HPLC under the following conditions: Apparatus: A liquid chromatograph equipped with variable wavelength UV detector; Column: Zorbax SB C18, 250 x 4.6mm, 5um or equivalent; Flow rate: 1.0 ml/min; Wavelength: 225 nm; Column temperature: 50°C; Injection volume: 5 uL; Run time: 45 min; Diluent: water:acetonitrile (80:20)v/v; Elution: Gradient; Mobile phase-A: Buffer; Mobile phase-B: Acetonitrile: water (90:10) v/v.

The particle size distribution of (2S,4S,5S,7S)-N-(2-carbamoyl-2-methylpropyl)-5-amino-4-hydroxy-2,7-diisopropyl-8-[4-methoxy-3-(3-methoxypropoxy)phenyl]-octanamide hemifumarate compound of formula-la is measured using Malvern Mastersizer.

The present invention is schematically represented as follows:

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-1: Preparation of 2-(7-methoxynaphthalen-l-yl)acetonitrile (Formula-4)
A solution of DDQ (126 ml) and toluene (1 lit) was added to a solution of 2-(l-hydroxy-7-methoxy-l,2,3,4-tetrahydronaphthalen-l-yl)acetonitrile compound of formula-2 (100 g) and toluene (4 lit) at 25-30°C under nitrogen atmosphere and heated to 60-65°C. The reaction mixture was stirred for 40 hours at 60-65°C and then cooled to 30-35°C. After completion of the reaction, the reaction mixture was filtered, sodium sulphite was added to the filtrate and both the toluene and aqueous layers were separated. Hydrochloric acid (50 ml) was added to the obtained toluene layer containing 2-(l-hydroxy-7-methoxy-l,2-dihydronaphthalen-l-yl)acetonitrile compound of formula-3 and stirred for 3 hours at 25-30°C. After completion of the reaction, sodium sulphite was added to the reaction mixture and both the toluene and aqueous layers were separated. Carbon (10 g) was added to the toluene layer and then stirred the reaction mixture. Filtered the reaction mixture through hyflow bed and the filtrate was distilled off completely under reduced pressure to get title compound as crude. Purity by HPLC: 97.78%

Example-2: Purification of 2-(7-methoxynaphthalen-l-yl)acetonitrile (Formula-4)
Methanol (200 ml) was added to the crude obtained in example-1 and heated to 40-50°C for dissolution.

The reaction mixture was cooled to 0-5°C and stirred for 1 hour at the same temperature. Filtered the solid, washed with methanol and then dried to get pure title compound. Yield: 60 g; MR: 83-85°C; purity by HPLC: 99.56%

Example-3: Preparation of 2-(7-methoxynaphthalen-l-yl)ethanamine hydrochloride (Formula-6)

2-(7-methoxynaphthalen-l-yl)acetonitrile compound of formula-4 (60 g) was added to a mixture of water (15 ml), Raney nickel (30 g) and methanolic ammonia (600 ml) at 25-30°C. Hydrogen gas (3-4 kg/cm2) was passed into the reaction mixture and stirred the reaction mixture for 10 hours at 45-55°C. After completion of the reaction, the reaction mixture was filtered through hyflow bed. Carbon (10 g) was added to the filtrate and then stirred. Filtered the reaction mixture on hyflow bed, the solvent from filtrate was distilled off completely under reduced pressure to get 2-(7-methoxynaphthalen-l-yl)ethanamine compound of formula-5 as a residue. Ethyl acetate (400 ml) was added to the obtained residue and then stirred at 25-30°C for 20 minutes. The reaction mixture was cooled to 0-10°C and then acidified with ethyl acetate-hydrochloride at 0-10°C, and stirred for 60 minutes at 10-20°C. Filtered the solid and washed with ethyl acetate to get title compound. Purity by HPLC: 99.61%

Example-4: Purification of 2-(7-methoxynaphthalen-l-yl)ethanamine hydrochloride (Formula-6)
The wet solid obtained in example-3 was added to a mixture of ethyl acetate (500 ml) and methanol (50 ml). The reaction mixture was heated to 50-55°C and then stirred for 45 minutes. The reaction mixture was cooled to 10-20°C and stirred for 60 minutes. Filtered the solid, washed with ethyl acetate and then dried to get pure title compound. Yield: 60 g; purity by HPLC: 99.81%.

The PXRD of the obtained compound is illustrated in figure-2.
Example-5: Preparation of N-[2-(7-methoxy-l-naphthyl)ethyl]acetamide (Formula-1)
A mixture of ethyl acetate (600 ml), water (120 ml), potassium carbonate (69.7 g) and 2-(7-methoxynaphthalen-l-yl)ethanamine hydrochloride compound of formula-6 (60 g) was cooled to 0-5°C. Acetyl chloride (30.5 g) was added to the reaction mixture and stirred for 2 1/2 hours at 0-5 °C. After completion of the reaction, water was added to the reaction mixture and both ethyl acetate and aqueous layers were separated. The ethyl acetate layer was washed with 2% hydrochloric acid solution followed by 5% sodium bicarbonate solution and water. Carbon (10 g) was added to the ethyl acetate layer at 25-30°C and then stirred for 15 minutes at 25-30°C. Filtered the reaction mixture through hyflow bed. The solvent from the filtrate was completely distilled off under the reduced pressure to get title compound.
Example-6: Preparation of crystalline form-I of N-[2-(7-methoxy-l-naphthyl)ethyl] acetamide (Formula-1)
Dimethylformamide (140 ml) was added to the compound obtained in example-5 and stirred for dissolution at 40-45°C. The reaction mixture was cooled to -35 to -30°C and then water was added to it and then stirred for 60 minutes at 0-10°C. Filtered the solid, washed with water and then dried to get title compound. Yield: 60 g; MR: 98-102°C; Purity by HPLC: 99.94%

Particle Size Distribution: D(0.1) is 16.064μm ; D(0.5) is 61.137 μm; D(0.9) is 152.343 urn
The PXRD of the obtained compound is matching with the crystalline form-I of Agomelatine and is illustrated in figure-1.

We claim:

1. An improved process for the preparation of N-[2-(7-methoxy-l-naphthyl)ethyl]acetamide compound of formula-1, comprising of:

a) Dehydrogenating the 2-(l-hydroxy-7-methoxy-l,2,3,4-tetrahydronaphthalen-l-yl) acetonitrile compound of formula-2

Formula-3 b) treating the compound of formula-3 in-situ with inorganic acid in toluene to provide 2-(7-methoxynaphthalen-l-yl)acetonitrile compound of formula-4,

Formula-4
c) optionally, purifying the compound of formula-4 from methanol to provide pure compound of formula-4,

d) reducing the compound of formula-4 with Raney nickel in presence of methanolic ammonia in water under hydrogen pressure to provide 2-(7-methoxynaphthalen-l-yl) ethanamine compound of formula-5,

Formula-5
e) treating the compound of formula-5 in-situ with ethyl acetate-hydrochloric acid in ethyl acetate to provide 2-(7-methoxynaphthalen-l-yl)ethanamine hydrochloride compound of formula-6,

Formula-1 h) optionally, purifying the compound of formula-1 by dissolving in dimethylformamide and followed by adding water to it to provide pure compound of formula-1.

2. A process according to claim 1, wherein
in step-a) DDQ used in the range of 0.5 to 5 molar equivalents to 1 mole of compound of formula-2; and toluene is used in the range of 20 to 60 volumes to per lg of compound of formula-2,

in step-b) inorganic acid used is selected from hydrochloric acid, hydrobromic acid and
sulfuric acid, in step-c) the methanol used in the range of 1 to 10 volumes per lg of compound of
formula-2, in step-d) the methanolic ammonia used in the range of 1 to 20 volumes per 1 g of
compound of formula-4, in step-f) the ratio of methanol to ethyl acetate used is in between 9.5:0.5 and 8:2.

3. A process for purification of 2-(7-methoxynaphthalen-l-yl)acetonitrile compound of
formula-4 comprising of:

a) Dissolving the 2-(7-methoxynaphthalen-l-yl)acetonitrile compound of formula-4 in metahnol at 40-50°C,

b) cooling the reaction mixture,

c) filtering the solid and then dried to get pure compound of formula-4.

4. A process for purification of 2-(7-methoxynaphthalen-l-yl)ethanamine hydrochloride
compound of formula-6, comprising of:

a) Adding the 2-(7-methoxynaphthalen-l-yl)ethanamine hydrochloride compound of formula-6 to a mixture of ethyl acetate and methanol,

b) heating the reaction mixture to 50-55°C,

c) stirring the reaction mixture,

d) cooling the reaction mixture,

e) filtering the solid and then dried to get pure compound of formula-6.

5. One pot process for the preparation of 2-(7-methoxynaphthalen-l-yl)acetonitrile
compound of formula-4, comprising of:

a) Dehydrogenating the 2-(l-hydroxy-7-methoxy-l,2,3,4-tetrahydronaphthalen-l-yl)acetonitrile compound of formula-2 with DDQ in toluene to provide 2-(l-hydroxy-7-methoxy-1,2-dihydronaphthalen-1 -yl)acetonitrile compound of formula-3,

b) treating the compound of formula-3 in-situ with inorganic acid in toluene to provide 2-(7-methoxynaphthalen-l-yl)acetonitrile compound of formula-4,

c) optionally, purifying the compound of formula-4 from methanol to provide pure compound of formula-
4.

6. One pot process for the preparation of 2-(7-methoxynaphthalen-l-yl)ethanamine
hydrochloride compound of formula-6, comprising of:
a) Reducing the 2-(7-methoxynaphthalen-1 -yl)acetonitrile compound of formula-4 with Raney nickel in presence of methanolic ammonia in water under hydrogen pressure to provide 2-(7-methoxynaphthalen-l-yl)ethanamine compound of formula-5,

b) treating the compound of formula-5 in-situ with ethyl acetate- hydrochloric acid in ethyl acetate to provide 2-(7-methoxynaphthalen-l-yl)ethanamine hydrochloride compound of formula-6,

c) optionally, purifying the compound of formula-6 from a mixture of ethyl acetate and methanol to provide pure compound of formula-6.

7. Use of inorganic acid as a dehydrating agent in the conversion of 2-(l-hydroxy-7-methoxy-l,2-dihydronaphthalen-l-yl)acetonitrile compound of formula-3 into 2-(7-methoxynaphthalen-l-yl)acetonitrile compound of formula-4.

8. A process for the preparation of 2-(l-hydroxy-7-methoxy-l,2-dihydronaphthalen-l-yl)acetonitrile compound of formula-3, comprising of dehydrogenating the 2-(l-hydroxy-7-methoxy-l,2,3,4-tetrahydronaphthalen-l-yl)acetonitrile compound of formula-2 with DDQ in toluene.

9. A process for the preparation of crystalline form-I of N-[2-(7-methoxy-1 -naphthyl)ethyl]
acetamide compound of formula-1, comprising of:

a) Dissolving the N-[2-(7-methoxy-1 -naphthyl)ethyl]acetamide compound of formula-1 in dimethylformamide by heating to 40-45°C,

b) cooling the reaction mixture to -35 to -30°C,

c) adding water to the reaction mixture,

d) stirring the reaction mixture,

e) filtering the solid and then dried to get crystalline form-I of compound of formula-1.

10. A crystalline form-M of 2-(7-methoxynaphthalen-l-yl)ethanamine hydrochloride compound of formula-6, which is characterized by its powder X-ray diffractogram having peaks at about 4.9, 14.9, 15.4, 16.0, 19.7, 21.4, 22.9, 23.2, 24.5,30.6 and 31.1 ± 0.2 degrees two-theta and substantially as shown in figure-2.