Efficient Synthesis of β-Aryl-γ-lactams and Their Resolution with (S)-Naproxen: Preparation of (R)- and (S)-Baclofen

Abstract

An efficient synthesis of enantiomerically-pure β-aryl-γ-lactams is described. The principal feature of this synthesis is the practical resolution of β-aryl-γ-lactams with (S)-Naproxen. The procedure is based on the Michael addition of nitromethane to benzylidenemalonates, which was easily obtained, followed by the reduction of the γ-nitroester in the presence of Raney nickel and the subsequent saponification/decarboxylation reaction. The utility of this methodology was highlighted by the preparation of enantiomerically-pure (R)- and (S)-Baclofen hydrochloride.

Keywords

• β-aryl-γ-lactams
• Michael addition
• resolution
• (S)-naproxen
• baclofen
• phenibut