Stereoselective synthesis of cis-4-(substituted) monobactams from ethyl acetoacetate

Abstract

The stereoselective synthesis of cis-3-amino-4-methyl-2-oxoazetidine-1-sulphonic acid (25) from ethyl acetoacetate is described. Nitrosation of this compound and reduction of the resulting oxime gave the corresponding amine, which after treatment with different acyl halides, yielded the acylamino derivatives (6)–(8). Condensation with p-anisidine gave the enamines (12)–(14), which were then reduced to the β-amino acid esters (15)–(17). Stereoselective cyclization with Grignard reagents as base, and appropriate deprotection and sulphonation of the resulting β-lactams (18)–(20), led to the title compounds.