Process for the preparation of(R)-Lacosamide

A process for synthesis of >99% ee enantio-pure (R)-Lacosamide from racemic butadiene monoepoxide and the said process comprising the five steps of:

• i. Deracemisation:
• of butadiene monoepoxide 2 with palladium catalyzed Trost's DYKAT in the presence of chiral ligand 1.2 mol % (R,R)-DACH and 0.4 mol % [η3-C3H5PdCl]2, phthalimide and base Na2CO3 at room temperature for period of 14 hours afforded asymmetric allylic alkylation (AAA) product phthaloyl alcohol
• ii. Methylation:
• preparing methyl ether (S)-4 from phthaloyl alcohol (S)-3 with methyl iodide under basic conditions in solvent at temperature in the range of 0° C. to Room Temperature for period of 3 hours;
• iii. Oxidative cleavage and acid formation:
• oxidative cleavage of the terminal double bond of (S)-4 in the presence of osmium tetraoxide and sodium periodate in solvent at temperature in the range of 0° C. to Room Temperature for period of 3 hours followed by oxidation with oxone in solvent at room temperature for period of 3 hours afforded (R)-5;
• iv. Amide formation:
• amide formation of (R)-5 as obtained in step (iii) with benzyl amine in the presence of isobutylchloroformate and N-methylmorpholine in solvent at temperature in the range of −78° C. to Room Temperature for period of 1 hour 1 hour afforded (R)-6;
• v. Phthalimide cleavage and acetylation:
• cleavage of phthalimide group of amide (R)-6 as obtained in step (iv) with hydrazine hydrate in solvent followed by N-acetylation in the presence of acetylating agent, base and solvent to obtain (R)-Lacosamide 1B.