Synthesis of [2H6]ceftazidime as a stable isotopically labeled internal standard

Ceftazidime is a third generation cephalosporin antibiotic that has activity against a wide range of Gram‐negative and Gram‐positive bacterial pathogens, including Escherichia coli and Pseudomonas aeruginosa. Stable isotope‐labeled ceftazidime was required for use as an internal standard in LC‐MS/MS assays, and a route was developed to make [2H6]ceftazidime in eight steps from the commercially available labeled starting material [2H7]isobutyric acid. A route has been developed to deliver the deuterium‐labeled cephalosporin antibiotic [2H6]ceftazidime in eight steps from commercially available [2H7]isobutyric acid. Several different approaches were investigated to couple the aminothiazole containing sidechain to the cephem core and coupling of an activated thioester of the sidechain to 7‐ACA proved to be successful.