Processes for reducing impurities in lacosamide

1. A process for the preparation of lacosamide comprising the steps of:

a) treating D-serine with a protecting reagent, wherein number of moles of the protecting reagent is less than the number of moles of D-serine, to obtain a compound of Formula V;

b) O-methylating the compound of Formula V obtained in step a) to produce a compound of Formula VI;

c) benzylaminating the compound of Formula VI to produce a compound of Formula VII;

d) deprotecting the compound of Formula VII to produce a compound of Formula IV; and

e) acetylating the compound of Formula IV in aqueous medium,

wherein R is a protecting group.

2. The process of claim 1 wherein the lacosamide prepared has levels of (2R)-2-(acetylamino)-3-(benzylamino)-3-oxopropyl acetate Impurity-A) that are undetectable by high performance liquid chromatography.

3. A process for the preparation of lacosamide comprising the steps of:

a) treating D-serine with a protecting reagent, wherein number of moles of the protecting reagent is less than the number of moles of D-serine, to obtain a compound of Formula V;

b) benzylaminating the compound of Formula V to produce a compound of Formula VIII;

c) O-methylating the compound of Formula VIII to produce a compound of Formula VII;

d) deprotecting compound of Formula VII to produce a compound of Formula IV; and

e) acetylating the compound of Formula IV in aqueous medium,

wherein R is protecting group.

4. The process of claim 3 wherein the lacosamide prepared has levels of (2R)-2-(acetylamino)-3-(benzylamino)-3-oxopropyl acetate (Impurity-A) that are undetectable by high performance liquid chromatography.

5. A process for reducing the content of (2R)-2-(acetylamino)-3-(benzylamino)-3-oxopropyl acetate (“Impurity-A”) of Formula II in lacosamide during the preparation of lacosamide, the process comprising a step of treating D-serine with a protecting reagent wherein the number of moles of the protecting reagent is less than the number of moles of D-serine

6. The process of claim 5 wherein the lacosamide prepared has levels of (2R)-2-(acetylamino)-3-(benzylamino)-3-oxopropyl acetate Impurity-A) that are undetectable by high performance liquid chromatography.

7. A process for reducing the content of (2R)-2-propanoylamino-N-benzyl-3-methoxypropionamide (“Impurity-B”) of Formula III in lacosamide during the preparation of lacosamide, the process comprising a step of acetylating the compound of Formula IV in aqueous medium

8. The process of claim 7 wherein lacosamide prepared has levels of (2R)-2-propanoylamino-N-benzyl-3-methoxypropionamide (Impurity-B) that are less than 0.01% as measured by high performance liquid chromatography.

9. The process of claim 1 wherein the lacosamide prepared has levels of (2R)-2-propanoylamino-N-benzyl-3-methoxypropionamide (Impurity-B) that are less than 0.01% as measured by high performance liquid chromatography.

10. The process of claim 3 wherein the lacosamide prepared has levels of (2R)-2-propanoylamino-N-benzyl-3-methoxypropionamide (Impurity-B) that are less than 0.01% as measured by high performance liquid chromatography.

11. The process of claim 1 wherein the protecting reagent comprises one or more of carbobenzyloxy chloride, tert.-butoxycarbonyl chloride, trityl chloride, and pthaloyl chloride.

12. The process of claim 3 wherein the protecting reagent comprises one or more of carbobenzyloxy chloride, tert.-butoxycarbonyl chloride, trityl chloride, and pthaloyl chloride.

13. The process of claim 5 wherein the protecting reagent comprises one or more of carbobenzyloxy chloride, tert.-butoxycarbonyl chloride, trityl chloride, and pthaloyl chloride.

14. The process of claim 1 wherein the protecting group comprises one or more of carbobenzyloxy, tert.-butoxycarbonyl, trityl, and pthaloyl.

15. The process of claim 3 wherein the protecting group comprises one or more of carbobenzyloxy, tert.-butoxycarbonyl, trityl, and pthaloyl.

16. The process of claim 5 wherein the protecting group comprises one or more of carbobenzyloxy chloride, tert.-butoxycarbonyl, trityl, and pthaloyl.

17. The process of claim 1 wherein treating D-serine with a protecting reagent comprises treating the D-serine with about 0.8 to 0.9 moles of the protecting reagent per mole of D-serine.