Cefuroxime Synthesis

Cefuroxime is a second-generation cephalosporin widely used in the treatment of bacterial infectious thanks to its effective, broad spectrum antibacterial activity against bacterials. Cefuroxime sodium (for the injection administration) and Cefuroxime Axetil (for the oral administration) are valuable in that they are highly resistant to β-lactamases due to the methoxyimino group present in the side chain at the 7-position of the cephalosporanic ring.The synthesis of cefuroxime discosed in U. S. Pat. No.3, 966, 717 and U.S. Pat. No. 3,974, 153 comprises 8 synthetic steps starting from 7ACA(7-amino cephalosporanic acid). Such high numbers of steps, which causes a low overall yield, is due to the introduction of two protective groups, the first (e.g. thienl acetyl) on the amine group function and the second (e. g. benzhydryl) on the 7-ACA acid function.Subsequently, processes starting from 7-ACA have been developed(Wilson, E.M. Chemistry and and industry 1984,217) which do not involve the use of protective groups and remarkably reduce the number of steps. In particular, the best process comprises 3 steps: 1. Conversion of 7-ACA into deacetyl-7-ACA;2.Acylation of the C-7 amino group;3. Carbamoylation of the C-3 alcohol group.In this paper, two methods which cefuroxime sodium was synthesized from 7-ACA were compared. Each of the two methods is suitable to get high quality product. 7-ACA was hydrolyzed in the mixture of methanol and water under low temperature, followed by acylation reaction to modify the C-3 site, and was isolated after being crystallized to obtain the key intermediate DCCFA, with the yield of more than 80%. DCCFA was then reacted with another reagent CSI to finish the carbamoylation reaction and cefuroxime acid was obtained, which was then converted into cefuroximesodium with the yield more than 90%.It is well known that the analysis of impurity spectrum and the source of each impurity is of great importance for the study of a drug. According to EP(European Pharmacopoeia), each impurity was discussed while the particular process was taken into consideration.At last, the structure of the title compound, cefuroxime sodium was confirmed by element analysis(EA), thermogravimetric analysis(TGA),infrared spectroscopy(IR), ultraviolet spectroscopy(UV), nuclear magnetic resonance spectroscopy (NMR, including H-NMR and C-NMR) and mass spectroscopy (MS). So, we can demonstrate that the compound obtained by said method is cefuroxime sodium.