Field of the Invention:

The present invention relates to an improved process for the preparation of (R)-N-benzyl-2-Acetamido-3-methoxypropionaniide (commonly known as Lacosamide) represented by the following structural formula-1

Lacosamide is an Anticonvulsant drug useful in the treatment of Central Nervous System disorders such as Epilepsy. This Drug is also useful in the treatment of pain particularly neuropathic pain such as Diabetic neuropathic painXacosamide is a functionalized aminoacid.This medication was formerly developed by UCB and sold under the Brand name VIMPAT®.

Background of the Invention:

Lacosamide and process for its preparation was disclosed in US 5773475. Different routes of synthesis for the preparation of Lacosamide have been reported in literature like US 5773475, US 6,048,899, US 2008/027137 and US 2009/143472 and Tetrahedron Asymmetry 1998, 9, 3841-3854.

In particular, the process disclosed in Tetrahedron Asymmetry 1998, 9, 3841- 3854 involves the reaction of D-Serine with Benzylchloroformate and MgO in diethylether to provide (R)-N-(benzyloxycarbonyl)serine, which on further treatment with benzylamine in presence of 4-methylmorpholine and isobutyl chloroformate in THF provides (R)-N-benzyl-2-N(Benzyloxycarbonyl)amino-3-hydroxypropionamide. Thus obtained hydroxy intermediate was methylated by treating with methyliodide in presence of silveroxide in acetonitrile to provide (R)-N-benzyl-2-N-(Benzyloxycarbonyl)amino-3- methoxypropionamide. Deprotection of the N-protecting group from the obtained methoxy derivative by hydrogenation in presence Pd/C catalyst in methanol provides (R)- N-benzyl-2-amino-3-propionamide, which on Acytylation with acetic anhydride in presence of DMAP and pyridine in THF gives Lacosamide.

The said process has number of disadvantages and hence is difficult to carry out in commercial scale. 1) It involves the usage of MgO and ether solvent for the N- protection of D-serine. The usage of ether solvent and MgO at commercial level is not recommendable. 2) It involves the usage of costly reagent like silver oxide and methyliodide for 0-methylation increases the cost of production and hence usage of the same in commercial scale is not possible. 3) Further it involves the usage of hydrogenation in presence of Pd/C catalyst for deprotection of N-protecting group to get lacosamide. The usage of Pd/C in commercial level is difficult to handle in safety aspect and increase the cost of production. Hence there is a need in the art for an improved process for the preparation of lacosamide which avoids all the problems mention here.

Brief Description of the Invention:

The first aspect of the present invention is to provide to an improved process for the preparation of (R)-N-benzyl-2-amino-3-methoxypropionamide compound of formula-6, which comprises of deprotection of N-protecting group from (R)-N-benzyl-2- N-(benzyloxycarbonyl)amino-3-methoxypropionamide compound of formula-5 to provide the compound of formula-6, characterized in that the deprotection is carried out in presence of suitable acid.

The second aspect of the present invention is to provide an improved process for the preparation of (R)-N-ben2yl-2-N-(benzyloxycarbonyl)amino-3-methoxy propionamide compound of formula-5, which comprises of reacting (R)-N-benzyl-2-N- (benzyloxycarbonyl)amino-3-hydroxypropionamide compound of formula-4 with a suitable methylating agent in a suitable solvent and in presence or absence of phase transfer catalyst.

The third aspect of the present invention is to provide an improved process for the preparation of lacosamide compound of formula-1, which comprises of the following steps,

a) reacting the D-serine compound of formula-2 with benzylchloroformate in a suitable inorganic base in a suitable solvent to provide the (R)-N-(benzyloxycarbonyl)serine compound of formula-3.

a) reacting the D-serine compound of formula-2 with benzylchloroformate in a suitable inorganic base in a suitable solvent to provide the (R)-N-(benzyloxycarbonyl)serine compound of formula-3,

b) reacting the compound of formula-3 with benzylamine in presence of isobutylchloroformate and N-methyl morpholine in a suitable solvent to provide the (R)-N-benzyl-2-N-(benzyloxycarbonyl)amino-3 -hydroxypropionamide compound of formula-4,

c) methylating the compound of formula-4 by treating with a suitable methylating agent in a suitable solvent and in presence or absence of phase transfer catalyst provides (R)-N-benzyl-2-N-(benzyloxycarbonyl)amino-3 -methoxypropionamide compound of formula-5,

d) treating the compound of formula-5 with a suitable acid in presence or absence of a solvent to provide the (R)-N-benzyl-2-amino-3-methoxypropionamide compound of fonnula-6,

e) reacting the compound of formula-6 with acetic anhydride in a suitable inorganic base in a suitable solvent to provide the lacosamide compound of formula-1,

f) optionally purifying the lacosamide using a suitable solvent gives highly pure lacosamide compound of formula-1.

The fourth aspect of the present invention is to provide one pot process for the preparation of lacosamide compound of formula-1, which comprises of reacting the (R)- N-benzyl-2-N-(benzyloxycarbonyl)amino-3-methoxypropionamide compound of formula-5 with a suitable acid in presence or absence of a solvent to provide the (R)-N- benzyl-2-amino-3-methoxypropionamide compound of formula-6, which on in-situ reaction with acetic anhydride in a suitable solvent to provide the lacosamide compound of formula-1,

Detailed Description of the Invention:

Unless otherwise specified, as used herein the present invention, the term "alkali metal hydroxides" refers to sodium hydroxide, potassium hydroxide and the like; "alkali metal carbonates" refers to sodium carbonate, potassium carbonate, cesium carbonate.
lithium carbonate and the like; "alkali metal bicarbonates" refers to sodium bicarbonate, potassium bicarbonate and the like;

Unless otherwise specified, as used herein the present invention, the term "phase transfer catalyst" refers to reagents selected from the group consisting of but not limited to tetra butyl ammonium bromide (TBAB), tetrapropyl ammonium bromide, tributyl benzyl ammonium bromide, tetraoctyl 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 and ethyl triphenyl phosphonium bromide; or alkali iodides like sodium iodide, potassium iodide and lithium iodide.
As used herein, the term "alcohol solvents" refers to methanol, ethanol, n-propanol, isopropanol and n-butanol and the like; "hydrocarbon solvents" refers to toluene, xylene, cyclohexane, hexane, heptane and the like; "polar aprotic solvents" refers to dimethylsulfoxide, dimethylacetamide, dimethyl formamide, tetrahydrofuran, acetonitrile and the like; "chloro solvents" refers to methylene chloride, ethylene dichloride, carbon tetra chloride, chloroform and the like; "nitrile solvents" refers to acetonitrile and the like;
As used here in the term "alcoholic solvent" is selected from methanol, ethanol, isopropanol, n-propanol, butanol and the like; the term "ester solvents" refers to ethyl acetate, methyl acetate, n-butyl acetate, isobutyl acetate, sec-butyl acetate, isopropyl acetate and the like; the term "hydrocarbon solvents" refers to toluene, xylene, cyclohexane, hexane, heptane and the like; the term "chloro solvents" refers to methylene chloride, ethylene dichloride, carbon tetra chloride, chloroform and the like; polar aprortic solvents refers to dimethylformamide, dimethylacetamide, dimethyl sulfoxide, tetrahydrofuran and the like; the term "nitrile solvents" refers to acetonitrile and the like; the term "polar solvent" refers to water and the like.
Accordingly the present invention provides an improved process for the preparation of lacosamide compound of formula-1 and its intermediates.

The first aspect of the present invention provides an improved process for the preparation of (R)-N-benzyl-2-amino-3-methoxypropionamide compound of formula-6,

which comprises of deprotection of N-protecting group from (R)-N-benzyl-2-N- (benzyloxycarbonyl)amino-3-methoxypropionamide compound of formula-5,

characterized in that the deprotection is carried out in presence of suitable acid selected from hydrochloric acid, sulphuric acid or phosphoric acid to provide the compound of formula-6. The said deprotection is carried out with or without usage of suitable solvents and the solvent is selected from polar solvents, alcohol solvents, chloro solvents and hydrocarbon solvents. The said reaction is carried out at a suitable temperature ranges between 20 to 80°C.
In a preferred embodiment, the process for the preparation of (R)-N-benzyl-2- amino-3-methoxypropionamide compound of formula-6 comprises treating the compound of formula-5 with hydrochloric acid at 40-45°C and isolating the formula-6 by methods known in the art.
The second aspect of the present invention provides an improved process for the preparation of (R)-N-benzyl-2-N-(benzyloxycarbonyl)amino-3-methoxypropionaniide compound of formula-5,

which comprises of reacting (R)-N-benzyl-2-N-(benzyloxycarbonyl)amino-3- hydroxypropionamide compound of formula-4

with a suitable methylating agent selected from dimethyl sulphate, methyl iodide or trimethyl phosphate in a presence of a suitable base selected from sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate or their aqueous solutions and a phase transfer catalyst in a suitable solvent selected from polar solvent, polar aprotic solvent, hydrocarbons or mixtures thereof to provide the (R)-N-benzyl-2-N-(benzyloxycarbonyl) amino-3-methoxypropionamide compound of formula-5.
In a preferred embodiment, the process for the preparation of (R)-N-benzyl-2-N- (benzyloxycarbonyl)amino-3-methoxypropionamide compound of formula-5 comprises of reacting (R)-N-benzyl-2-N-(benzyloxycarbonyl)amino-3 -hydroxypropionamide compound of formula-4 with dimethyl sulphate in presence of aqueous sodium hydroxide, tetra butyl ammonium bromide (TBAB) in water to provide the compound of formula-5.
The third aspect of the present invention provides an improved process for the preparation of lacosamide compound of formula-1, which comprises of the following steps,
a) Reacting the D-serine compound of formula-2

with benzylchloroformate in a suitable alkalimetal carbonate or hydroxide bases in a suitable polar solvent to provide the (R)-N-(benzyloxycarbonyl)serine compound of formula-3,

b) reacting the compound of formula-3 with benzylamine in presence of isobutylchloroformate and N-methyl morpholine in a suitable solvent selected from polar aprotic solvent and chlorosolvents or mixtures thereof to provide the (R)-N-benzyl-2-N-(benzyloxycarbonyl)amino-3-hydroxypropionamide compound of formula-4,
c) methylating the compound of formula-4 by treating with a suitable methylating agent like dimethylsulphate, methyliodide and trimethylphosphate in a presence of a suitable base selected from sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate or their aqueous solutions and a phase transfer catalyst in a suitable solvent selected from polar solvent, polar aprotic
solvents, hydrocarbons or mixtures thereof provides (R)-N-ben2yl-2-N- (benzyloxycarbonyl) amino-3-methoxypropionamide compound of fonnula-5,

d) deprotecting the N-protection group from the compound of fonnula-5 with a suitable acid selected from hydrochloric acid, sulphuric acid or phosphoric acid vdth or without the usage of solvent selected from alcohol solvents, chloro solvents and hydrocarbon solvents or mixtures thereof to provide the (R)-N-benzyl-2-amino-3- methoxypropionamide compound of formula-6,
e) reacting the compound of formula-6 with acetic anhydride in a suitable solvent selected from chloro solvents, ester solvent or hydrocarbon solvent to provide the lacosamide compound of formula-1,
f) optionally purifying the lacosamide using a suitable solvent selected from chloro solvents or ester solvent or mixtures thereof provides highly pure lacosamide compound of formula-1.
In a preferred embodiment of the present invention, improved process for the
preparation of lacosamide compound of formula-1 comprises of the following steps,
a) Reacting the D-serine compound of fonnula-2 with benzylchloroformate in presence of sodium bicarbonate in water to provide the (R)-N-(benzyloxycarbonyl)serine compound of formula-3,
b) reacting the compound of formula-3 with benzylamine in presence of isobutylchloroformate and N-methyl morpholine in methylene chloride to provide the
(R)-N-benzyl-2-N-(benzyloxycarbonyl)ainino-3-hydroxypropionamide compound of formula-4,
c) methylating the compound of formula-4 by treating with dimethylsulphate in presence of aqueous sodium hydroxide, tetra butyl ammonium bromide (TBAB) in water provides (R)-N-benzyl-2-N-(benzyloxycarbonyl)amino-3-methoxy propionamide compound of formula-5,
d) treating the compound of formula-5 with hydrochloric acid to provide the (R)-N-benzyl-2-amino-3-methoxypropionamide compound of formula-6,
e) reacting the compound of fonnula-6 with acetic anhydride in methylene chloride to provide the lacosamide compound of formula-1,
f) purifying the lacosamide using a ethyl acetate provides highly pure lacosamide compound of formula-1.
The fourth aspect of the present invention provides one-pot process for the
preparation of lacosamide compound of formula-1, which comprises of
a) treating the (R)-N-benzyl-2-N-(benzyloxycarbonyl)amino-3-methoxy propionamide compound of formula-5 with a suitable acid selected from hydrochloric acid, sulphuric acid or phosphoric acid or its aqueous solutions,
b) heating the reaction mixture and stirring,
c) quenching the reaction mixture with water and
d) basifying the reaction mixture with suitable aqueous alkali metal hydroxide or alkali metal carbonates/bicarbonate bases,
e) extracting the reaction mixture into suitable chlorosolvent, ester solvent or hydrocarbon solvent,
f) cooling the reaction mixture,
g) treating the extracted reaction mixture with acetic anhydride,
h) washing the reaction mixture with aqueous basic solution,
i) distilling off the solvent from the reaction mixture under reduced pressure,
j) crystallizing the obtained crude from ester solvents.
In a preferred embodiment, one-pot process for the preparation of lacosamide
compound of formula-1 comprises of
a) treating the (R)-N-benzyl-2-N-(benzyloxycarbonyl)amino-3-methoxy propionamide compound of formula-5 with hydrochloric acid,
b) heating the reaction mixture to 40-45°C and stirring for 45 minutes,
c) quenching the reaction mixture with water and
d) basifying the reaction mixture aqueous sodium hydroxide solution,
e) extracting the reaction mixture into methylene chloride,
f) cooling the reaction mixture to 0-5°C,
g) treating the extracted reaction mixture with acetic anhydride,
h) washing the reaction mixture with aqueous sodiumbicarbonate followed by water,
i) distilling off methylene chloride from the reaction mixture under reduced pressure, j) crystallizing the obtained crude from ethyl acetate to provide the lacosamide.
The (R)-N-benzyl-2-amino-3-methoxypropionamide can also be isolated as its organic acid addition salts and is prepared by treating the (R)-N-benzyl-2-amino-3- methoxypropionamide compound of formula-6 with a suitable organic acid selected from oxalic acid, succinic acid, ftimaric acid, malonic acid, malic acid, maleic acid, tartaric acid, citric acid, methanesulfonic acid, paratoluene sulfonic acid and acetic acid in a suitable solvent to provide the corresponding salt of (R)-N-benzyl-2-amino-3- methoxypropionamide. These salts can be obtained in either crystalline or amorphous form. Thus obtained (R)-N-benzyl-2-amino-3-methoxypropionamide organic acid addition salts are used to prepare highly pure compound of fonnula-6 and lacosamide compound of formula-1.
The present invention schematically represented as follows:


The following are the possible impurities which are formed in the preparation of lacosamide.

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 (R)-N-(benzyloxycarbonyl)serine of Formula 3:
Sodium bicarbonate (240 g) was added to a mixture of D-serine (100 g) and water (800 ml) at 0.5°C. Benzylchloroformate (50 % solution in toluene)(480 ml) was added to the reaction mixture and stirred for 10 hours at 0-5°C. The organic and aqueous layers were separated and washed the aqueous layer with toluene. Aqueous layer pH was adjusted to 1.5 with hydrochloric acid and extract the reaction mixture in to ethylacetate. Distilled off the solvent from the extracted reaction mixture imder reduced pressure to get the title compound. Yield: 195 grams

Example-2: Preparation of (R)-N-benzyl-2-N-(benzyIoxycarbonyI)amino-3- hydroxypropionamide compound of formula-4:
Isobutylchloroformate (17 ml) was added to the pre cooled mixture of (R)-N- (benzyloxycarbonyl)serine(25 g) and methylene chloride (312 ml) at below -65 to -70°C and stirred for 15 mins. N-Methylmorpholine (16.2 ml) was added at -70°C and stirred for 30min. Benzylamine(14.3ml) was added to the reaction mixture and stirred for 5 hours at -70''C. The reaction mixture temperature was raised to 20-25°C and filtered the undissolved salts then washed with methylene chloride. The solvent from the reaction mixture was distilled off completely under reduced pressure at 40-45°C to get the title compound. Yield: 30 grams
Example-3: Preparation of 2-N-(benzyloxycarbonyl) amino-3-methoxy propionamide compound of formula-5:
Sodium hydroxide (3 ml, 20%) was added to a mixture of (R)-N-benzyl-2-N- (benzyloxycarbonyl)amino-3-hydroxy propionamide (5 g) in water (50 ml) and n- Tetrabutylammoniumbromide(TBAB) (0.2g) at 0-5®C. Dimethylsulphate (5.7ml) and
50%NaOH(9.6ml) were simultaneously added to the reaction mixture at 0-5®C and stirred for 3 hours. The solid obtained was filtered off, washed with water and then dried at 30- 35°C to get the title compound. Yield: 3 grams
Example-4: Preparation of 2-N-(benzyloxycarbonyl) amino-3-methoxy propionamide compound of formuIa-5:
The title compound is prepared in a similar manner to example-3 except that cyclohexane used in place of water. Yield: 2.8 grams
Exampie-4: Preparation of (R)-N-benzyI-2-amino-3-methoxypropionamide compound of formuIa-6
A mixture of 2-N-(benzyloxycarbonyl) amino-3-methoxy propionamide (15 grams) and concentrated hydrochloric acid (150 ml) was heated to 40-45°C and stirred for 45 mins. The reaction mixture was cooled to 0-5°C. Water (75 ml) was added to the reaction mixture and basified with aqueous sodium hydroxide solution. The reaction mixture is extracted into methylene chloride. The methylene chloride layer containing layer (R)-N-benzyl-2-amino-3-methoxypropionamide compound of fonnula-6 used directly in next step.
Example-5: Preparation of lacosamide compound of formuIa-1:
Acetic anhydride (3.57 g) was added to methylene chloride layer containing (R)- N-benzyl-2-amino-3-methoxypropionamide (150 ml) obtained as per example-4 at 0-5^C and stirred for an hour. The reaction mixture was washed with sodiumbicarbonate solution followed by water. The reaction mixture was dried over sodiumsulphate and the solvent was distilled off xmder reduced pressure. Ethyl acetate (30 ml) was added and distilled off completely. Ethylacetate (60 ml) was added to the residue and heated to reflux temperature. The reaction mixture was cooled to 45-50°C and stirred for 4 hours. The reaction mixture was further cooled to 0-5° and stirred for 45 mins. The solid obtained was filtered off, washed with ethyl acetate and dried to get the title compound. Yield: 6 grams

Example-6: One pot process for lacosamide:
A mixture of 2-N-(benzyloxycarbonyl) amino-3-methoxy propionamide (15 grams) and concentrated hydrochloric acid (150 ml) was heated to 40-45°C and stirred for 45 mins. The reaction mixture was cooled to 0-5°C. Water (75 ml) was added to the reaction mixture and basified with aqueous sodium hydroxide solution. The reaction mixture is extracted into methylene chloride. Acetic anhydride (3.57 g) was added to reaction mixture at 0-5 °C and stirred for an hour. The reaction mixture was washed with sodiumbicarbonate solution followed by water. The reaction mixture was dried over sodiumsulphate and the solvent was distilled off under reduced pressure. Ethyl acetate (30 ml) was added and distilled off completely. Ethylacetate (60 ml) was added to the residue and heated to reflux temperature. The reaction mixture was cooled to 45-50°C and stirred for 4 hours. The reaction mixture was further cooled to 0-5° and stirred for 45 mins. The solid obtained was filtered off, washed with ethyl acetate and dried to get the title compound. Yield: 5.6 grams

We claim:
1. An improved process for the preparation of (R)-N-ben2yl-2-amino-3- methoxypropionamide compound of formula-6,

which comprises of deprotection of N-protecting group from (R)-N-benzyl-2-N- (benzyloxycarbonyl)amino-3-methoxypropionamide compound of formula-5,

characterized in that the deprotection is carried out in presence of suitable acid selected from hydrochloric acid, sulphuric acid or phosphoric acid with or without usage of suitable solvents and the solvent is selected from alcohol solvents, chloro solvents and hydrocarbon solvent to provide the compound of formula-6.

2. A process for the preparation of (R)-N-benzyl-2-amino-3-methoxypropionamide compound of formula-6 comprises of treating the compound of formula-5 with hydrochloric acid at 40-45°C to provide the compound of formula-6.

3. An improved process for the preparation of (R)-N-benzyl-2-N- (benzyloxycarbonyl)amino-3-methoxypropionamide compound of formula-5,

which comprises of reacting (R)-N-benzyl-2-N-(benzyloxycarbonyl)amino-3- hydroxypropionamide compound of formula-4

with a suitable methylating agent dimethyl sulphate, methyl iodide or trimethyl phosphate in a presence of a suitable base selected from sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate or their aqueous solutions and a phase transfer catalyst in a suitable solvent selected from polar solvent, polar aprotic solvents, hydrocarbons or mixtures thereof to provide the (R)-N-benzyl-2-N-(benzyloxycarbonyl) amino-3-methoxypropionamide compound of formula-5.

4. A process for the preparation of (R)-N-benzyl-2-N-(benzyloxycarbonyl)amino-3- methoxypropionamide compound of formula-5 comprises of reacting (R)-N-benzyl- 2-N-(benzyloxycarbonyl)amino-3-hydroxypropionamide compound of formula-4 with dimethyl sulphate in presence of aqueous sodium hydroxide, TBAB in water to provide the compound of formula-5.

5. An improved process for the preparation of lacosamide compound of formula-1,

which comprises of the following steps,

a) Reacting the D-serine compound of formula-2

with benzylchloroformate in a suitable alkalimetal carbonate or hydroxide bases in a suitable polar solvent to provide the (R)-N-(benzyloxycarbonyl)serine compound of formula-3,

b) reacting the compound of formula-3 with benzylamine in presence of isobutylchloroformate and N-methyl morpholine in a suitable solvent selected from polar aprotic solvent and chlorosolvents or mixtures thereof to provide the (R)-N-benzyl-2-N-(benzyloxycarbonyl)amino-3 -hydroxypropionamide compound of formula-4,

c) methylating the compound of formula-4 by treating with a suitable methylating agent like dimethylsulphate, methyliodide and trimethylphosphate in a presence of a suitable base selected from sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate or their aqueous solutions and a phase transfer catalyst in a suitable solvent selected from polar solvent, polaraprotic solvents, hydrocarbons or mixtures thereof provides (R)-N-benzyl-2- N-(benzyloxycarbonyl) amino-3-methoxypropionamide compound of formula-5,

d) deprotecting the N-protection group from the compound of formula-5 with a suitable acid selected from hydrochloric acid, sulphuric acid or phosphoric acid with or without the usage of solvents selected from alcohol solvents, chloro
solvents and hydrocarbon solvents to provide the (R)-N-benzyl-2-amino-3- methoxypropionamide compound of formula-6,

e) reacting the compound of fonnula-6 with acetic anhydride in a suitable solvent selected from chloro solvents, ester solvent or hydrocarbon solvent to provide the lacosamide compound of formula-1,

f) optionally purifying the lacosamide using a suitable solvent selected from chloro solvents or ester solvent or mixtures thereof provides highly pure lacosamide compound of formula-1.

6. An improved process for the preparation of lacosamide compound of formula-1
comprises of the following steps,

a) Reacting the D-serine compound of formula-2 with benzylchloroformate in presence of sodium bicarbonate in water to provide the (R)-N- (benzyloxycarbonyl)serine compound of formula-3,

b) reacting the compound of formula-3 with benzylamine in presence of isobutylchloroformate and N-methyl morpholine in methylene chloride to provide the (R)-N-benzyl-2-N-(benzyloxycarbonyl)amino-3-hydroxypropionamide compound of formula-4,

c) methylating the compound of formula-4 by treating with a dimethylsulphate in a presence of aqueous sodium hydroxide, TBAB in water provides (R)-N-benzyl-2- N-(benzyloxycarbonyl) amino-3-methoxypropionamide compound of formula-5,

d) treating the compound of formula-5 with hydrochloric acid to provide the (R)-N- benzyl-2-amino-3-methoxypropionamide compound of formula-6,

e) reacting the compound of formula-6 with acetic anhydride in methylene chloride to provide the lacosamide compound of formula-1,

f) purifying the lacosamide using a ethyl acetate provides highly pure lacosamide compound of formula-1.

7. A process which comprises of reacting the D-serine compound of formula-2 with benzylchloroformate in presence of alkali metal carbonates/bicarbonates in a suitable solvent to provide the (R)-N-(benzyloxycarbonyl)serine compound of formula-3.

8. A process according to claim 7, where in the alkalimetal carbonate is selected from sodium carbonate, potassium carbonate, sodium bicarbonate and potassium bicarbonate; and the suitable solvent is water.

9. One-pot process for the preparation of lacosamide compound of formula-1,

which comprises of

a) treating the (R)-N-benzyl-2-N-(benzyloxycarbonyl)amino-3-methoxy propionamide compound of formula-5 with a suitable acid selected from hydrochloric acid, sulphuric acid or phosphoric acid or its aqueous solutions,

b) heating the reaction mixture and stirring,

c) quenching the reaction mixture with water and

d) basifying the reaction mixture with suitable aqueous alkali metal hydroxide or alkali metal carbonates/bicarbonate bases,

e) extracting the reaction mixture into suitable chlorosolvent or hydrocarbon solvent,

f) cooling the reaction mixture,

g) treating the extracted reaction mixture with acetic anhydride,

h) washing the reaction mixture with aqueous basic solution,

i) distilling off the solvent from the reaction mixture under reduced pressure, j) crystallizing the obtained crude from ester solvents.

10. One-pot process for the preparation of lacosamide compound of formula-1 comprises of

a) treating the (R)-N-benzyl-2-N-(benzyloxycarbonyl)amino-3-methoxy propionamide compound of formula-5 with hydrochloric acid.

b) heating the reaction mixture to 40-45°C and stirring for 45 minutes,

c) quenching the reaction mixture with water and

d) basifying the reaction mixture aqueous sodium hydroxide solution,

e) extracting the reaction mixture into methylene chloride,

f) cooling the reaction mixture to 0-5°C,

g) treating the extracted reaction mixture with acetic anhydride,

h) washing the reaction mixture with aqueous sodiumbicarbonate followed by water,

i) distilling off methylene chloride from the reaction mixture under reduced pressure,

j) crystallizing the obtained crude from ethyl acetate to provide the lacosamide