头孢替唑钠的合成工艺研究

目的 改进头孢替唑钠的合成工艺。 方法 以7-氨基头孢烷酸 （7-ACA）为起始原料，与1H-四氮唑乙酸-1,3,4-噻二唑-2-硫酯（2）反应得中间体7-（1H-四氮唑乙酰氨基）头孢烷酸（3），以甲磺酸为催化剂，3与2-巯基-1,3,4-噻二唑经亲核取代反应制得头孢替唑酸（4），4与碳酸氢钠反应得到目标化合物。结果与结论 目标化合物的结构经¹H-NMR 和 HR-MS 确证，改进后的合成工艺操作简便，总收率达69.6%，降低了成本，有利于工业化生产。

Improved synthesis of ceftzole sodium

Ceftezole sodium is a kind of β-lactam antibiotics for the treatment of inflammation caused by bacteria.Its synthetic route was optimized and improved.The target compound was obtained from 7-ACA as starting material by acylation,nucleophilic substitution,salification.7-ACA was reacted with active ester（2） under certain conditions to give the key intermediate of 7-tetrazole acetyl aminocephalosporanic acid（3）.With mesylate as catalyst,the compound 3 was reacted with 2-mercapto-1,3,4-thiadiazole in acetic acid to give ceftezole acid（4）.Then ceftezole acid was changed into sodium salt（1） with sodium bicarbonate by salification.The target compound was identified by 1H-NMR and HR-MS and the overall yield was raised to 69.6% with 98.5% content.The improved process reduced the use of raw materials with relatively conve-nient operation procedure and was more suitable for large-scale industrial production.