Process for preparing (R)-2-acetamido-N-benzyl-3-methoxy-propionamide

1. A process for the preparation of lacosamide compound of Formula-1,

the process comprising:

a) reacting a compound of Formula-10

with acetic anhydride in a solvent or mixture of solvents to produce a compound of Formula-2; and

b) O-methylating the compound of Formula-2 with a methylating agent in presence of a base selected from an organic base or inorganic base or its aqueous solution in a solvent or solvent mixture and in presence or absence of phase transfer catalyst to produce lacosamide compound of Formula-1, wherein

the organic base is selected from triethylamine, triethanolamine, diisopropylethylamine or di-n-propylamine, or a mixture of the foregoing; and

the inorganic base is selected from an alkali metal hydroxide, an alkali metal carbonate, an alkali metal bicarbonate or an alkali metal alkoxide, or a mixture of the foregoing.

2. The process according to claim 1 , wherein the methylating agent is selected from dimethylsulfate, methyl iodide and trimethylphosphate.

3. The process of claim 1 , wherein the compound of Formula-10

is prepared by the process comprising:

a) esterifying a compound of Formula-3

with an alcoholic solvent in presence of dry HCl to produce a compound of Formula-9

wherein R is C 1-6 alkyl; and

b) reacting the compound of Formula-9 with benzylamine in a suitable solvent or mixture of solvents to produce compound of Formula-10.

4. The process of claim 1 , further comprising:

a) suspending the lacosamide compound of Formula-1 in ethyl acetate, thereby forming a mixture;

b) stirring the mixture for an hour at 25-35° C.;

c) cooling the mixture to 0-5° C. and stirring for an hour, thereby forming a solid;

d) filtering the solid and washing with chilled ethyl acetate; and

e) drying the solid to get lacosamide compound of Formula-1 having a purity of greater than 99.50% by high-performance liquid chromatography (HPLC).

5. The process of claim 1 , wherein step (b) comprises O-methylating the compound of Formula-2 with dimethyl sulfate in presence of aqueous sodium hydroxide solution and tetrabutylammonium bromide in toluene to provide the lacosamide compound of Formula-1.

6. The process of claim 1 , wherein step a) further comprises:

(i) dissolving or suspending the compound of Formula-2 in a mixture of methylene chloride and methyl tertiary butyl ether to form a reaction mixture;

(ii) stirring the reaction mixture for an hour at 25-35° C.;

(iii) filtering the precipitated solid from step (ii) and washing with methyl tertiary butyl ether; and

(iv) drying the solid from step (iii) to get pure compound of Formula-2.

7. The process according to claim 1 , wherein step b) is carried out in absence of the phase transfer catalyst.

8. The process according to claim 1 , wherein step b) is carried out at a temperature of from 5° C. to 10° C.