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

Molecules. 2015 Dec 10;20(12):22028-43. doi: 10.3390/molecules201219830.

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: (S)-naproxen; Michael addition; baclofen; phenibut; resolution; β-aryl-γ-lactams.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Baclofen / chemical synthesis*
  • Catalysis
  • Lactams / chemical synthesis*
  • Naproxen / chemistry*
  • Stereoisomerism

Substances

  • Lactams
  • Naproxen
  • Baclofen