Process for producing lacosamide

1. A method for producing (R)-2-acetamido-N-benzyl-3-methoxypropionamide comprising methylating (R)-2-acetamino-2-N-benzyl-3-hydroxy-propionamide (V), wherein the methylation is carried out at a temperature below 20° C.

2. A process according to claim 1 , wherein the temperature during methylation is maintained below 10° C.

3. A process according to claim 1 , wherein the temperature during methylation is maintained below 5° C.

4. A process according to claim 1 , further comprising dimethyl sulfate as a methylation agent.

5. A process according to claim 1 , further comprising methyl iodide, methyl toluenesulfonate or another methyl arylsulfonate, a methyl alkylsulfonate, or trimethylphosphonate as a methylation agent.

6. A process according to claim 1 , wherein the ee of the isolated (R)-2-acetamino-2-N-benzyl-3-methoxy-propionamide is greater than or equal to 97%.

7. A process according to claim 1 , wherein the ee of the isolated (R)-2-acetamino-2-N-benzyl-3-methoxy-propionamide is greater than or equal to 99%.

8. A process according to claim 1 , wherein a phase transfer catalyst is present during methylation.

9. A process according to claim 1 , wherein an alkali metal hydroxide base is present.

10. A process according to claim 1 , wherein (R)-2-acetamino-2-N-benzyl-3-hydroxy-propionamide (V) is produced via de-protection and acetylation of (R)-boc-2-amino-N-benzyl-3-hydroxy-propionamide (III) and intermediate (R)-2-amino-N-benzyl-3-hydroxy-propionamide (IV) is not isolated.

11. A process according to claim 10 , wherein (R)-N-(tert-butoxycarbonyl)-2-amino-N-benzyl-3-hydroxy-propionamide (III) is produced by coupling (R)-N-(tert-butoxycarbonyl)-serine and benzylamine using 2,4,6-tripropyl-2,4,6-trioxo-1,3,5,2,4,6-trioxatriphosphorinane as a coupling reagent in the presence of a base.