Carboxylic sulfonic mixed anhydrides: General utility and application to the synthesis of ceftazidime

Article abstract of DOI:10.1016/S0040-4020(01)80340-9

A high-yielding acylation process which utilizes a mixed anhydride of the type RCO₂SO₂CH₃ for the synthesis of the cephalosporin ceftazidime is detailed. The mixed anhydride is conveniently prepared by addition of methanesulfonyl chloride to the triethylammonium salt of the acid 2a. Although known for some time, these anhydrides have not been used often in acylations. This lack of general utility is explained by side reactions, especially formation of the carboxylic symmetric anhydride in sterically unhindered systems.