Synthesis of a Glycine Antagonist

Abstract

The target molecule is an orally available glycine antagonist that is under development for the treatment of nicotine craving. The route depicted produced more than 300 kg of the target with a purity of >99.9%. The high efficiency of the enzymatic resolution of rac-F (E > 500) using an immobilized lipase from Mucor miehei was further enhanced by the easy recycling afforded by the epimerization of the unwanted enantiomer (S)-F. A total of 600 kg of (R)-F with a chiral purity of 99.7% was prepared by this route.