N-methylative aziridine ring opening and the synthesis of (S)-3-methylamino-3-[(R)-pyrrolidin-3-yl]propanenitrile

Abstract The preparation of ( S )-3-methylamino-3-[( R )-pyrrolidin-3-yl]propanenitrile ( 1 ), a key fragment of fluoroquinolone antibiotic PF-00951966 and others was achieved by N -methylative aziridine ring opening, addition of methyl group at the ring nitrogen, and ring-opening via a cyanide nucleophile in a single operation starting from bicyclic ( R )-2-[( R )-pyrrolidine-3-yl]aziridine. The starting compound was elaborated from stereoselective conjugate addition of nitromethane to ( R )-aziridine-2-yl acrylate followed by selective reduction without breaking the aziridine ring.