Improved synthesis scheme for lacosamide

摘要

Disclosed is a method of producing (R)-2-acetamido-N-benzyl-3-methoxypropionamide (Iacosamide) comprising the O-methylation of a compound of formula I to produce a compound of formula II wherein Rx is an N-protecting group, and wherein the compound of formula II is reacted with benzylamine to give the compound of formula III, and the protecting group Rx is replaced with methyl carbonyl to give (R)-2- acetamido-N-benzyl-3-methoxypropionamide,characterised in that the O-methylation is being carried out in a one-step reaction and wherein the compound of formula II is obtained as an R-enantiomer of at least 88% purity and the method is performed either (a) as a phase transfer catalysis or (b) by adding a methylation agent and an organo lithium compound to the compound of formula I.