Synthesis of (2RS, 5RS, 6SR)-3-methoxycarbonyl-7-oxo-6-phenoxyacetamido-1-azabicyclo[3.2.0]hept-3-ene-2-carboxylic acid

Abstract

Addition of the mixed anhydride derived from azidoacetic acid and trifluoroacetic anhydride to benzyl 2-(N-cinnamylideneamino)-3,3-dimethylacrylate (19) in the presence of triethylamine afforded (3RS, 4SR)-3-azido-1-(1-benzyloxycarbonyl-2-methylprop-1-enyl)-4-styrylazetidin-2-one (20), which was converted into (3RS, 4SR)-1-(1-benzyloxycarbonyl-2-methoxycarbonyl-2-triphenylphosphoranylidene-ethyl)-3-phenoxyacetamido-4-styrylazetidin-2-one (29) and (3RS, 4RS)-1-(1-benzyloxycarbonyl-2-methoxycarbonyl-2-triphenylphosphoranylidene-ethyl)-4-dimethoxymethyl-3-phenoxyacetamidoazetidin-2-one (30). Ozonolysis of compound (29) in the presence of trifluoroacetic acid gave (2RS, 5RS, 6SR)-benzyl 3-methoxycarbonyl-7-oxo-6-phenoxyacteamido-1-azabicyclo[3.2.0]hept-3-ene-2-carboxylate (31). The ester (31) was also prepared by trifluoroacetic acid treatment of the phosphorane (30).

Hydrogenation of compound (31) over 10% Pd–C afforded (2RS, 5RS, 6SR)-3-methoxycarbonyl-7-oxo-6-phenoxyacetamido-1-azabicyclo[3.2.0]hept-3-ene-2-carboxylic acid (35), which was antibacterially active.