Lacosamide total synth

12 July 2014 - Orgo

lacosamide  Lacosamide is a drug for the treatment of epilepsy. There is no shortage of interest in the production of this compound. The latest academic contribution originates from Sebastian Stecko as single author here. The selected raw material was ethyl lactate 1. Several steps down the road allyl alcohol 2 was reacted with trichloroacetyl isocyanate in methanol to form carbamate 3. Dehydration with trifluoroacetic acid/ triethylamine in THF formed the corresponding cyanate which by a cyanate-to-isocyanate sigmatropic rearrangement first formed the isocyanate and then by addition of methylmagnesium chloride the acetamide 5, all in one step. The double bond was then cleaved with ruthenium chloride/ sodium periodate to carboxylic acid 6. reaction with isobutyl chloroformate / N-methyl morpholine produced lacosamide 7.