ABSTRACT
This process supported Phase-Ill development, NDA/MAA filing and approval, and launch of aztreonam. It was not, however, as convergent as we would have liked. A major step towards a more convergent synthesis was taken by using the a-ketoacid 16 (Scheme 7). Appropriate commercial arrangements were reached that allowed us access to this substance. Coupling of 16 with 12, followed by oximation/deprotection, provided a more convergent, “efficient” process to aztreonam. Since the deprotection of the formamide moiety could be accomplished with mineral acid, it was actually a superior procedure to the more convergent process utilizing benzyhydryl ester 13 (one less step but requiring trifluoroacetic acid). The one remaining vexing issue was the 85/15 ratio of Z/E isomers formed in the oxidation step.
