Economic kilogram-scale synthesis of the novel antiepileptic drug brivaracetam utilizing porcine pancreatic lipase

Abstract

A facile synthesis of brivaracetam, a mainstream antiepileptic drug, is described employing direct de-esterification, enzymatic hydrolysis by porcine pancreatic lipase, and a cyano hydrolysis–cyclization cascade as key steps. The concise process has been applied to the kilogram scale with extremely low cost owing to the much cheaper porcine pancreatic lipase (PPL), reuse of the unwanted enantiomer and excellent yields of each step.