Cefepime Hydrochloride Synthesis Process Improvement

Cefepime Hydrochloride (Cefepime Hydrochloride) is the1990s by the U.S. companyBristol-Myers Squibb R&D,1993listed as the fourth-generation cephalosporins are listedfirst, with broad spectrum antimicrobial activity of the characteristics of high. Manysynthetic methods reported in the literature, yet the card from starting materials, there aretwo: the first one is to GCLE material;7-ACA isthe second. Long synthetic route toGCLE start, you need to replace、 de-protection and other multi-step reaction.7-ACA asstarting material in order to prevent the generation of isomerization need to use smallpolarity as freon or cyclopentane and iodo silylation reagent, the yield is low, the solventrecovery difficult. In this paper the synthesis method is optimized, methylene chloride as asolvent to choose a single, specific conditions controlling the moisture control system andmethod of the reaction, to ensure that after completion of the silylation reaction, and iodoprotection, was added N-methyl-substituted pyrrolidine, will not happen△-isomerization. Cefepime Hydrochloride step to get the key intermediate7-a分钟o-3-(1-methyl l-tetrahydropyrrole) methyl-3-cephem-4-carboxylic acid hydrochloride(7-MPCA), then with AE-active ester condensation cefepime hydrochloride crude productwas recrystallized cefepime hydrochloride. High performance liquid chromatographypurity greater than99.5%of the total yield of70%. Finally, elemental analysis (EA),infrared chromatography (IR), nuclear magnetic resonance analysis (1HNMR) and massspectrometry (MS) and other means, to deter分钟e the structure of the resulting product,the resulting product was confirmed cefepime hydrochloride.