头孢唑肟酸合成方法研究

Studies on the synthesis of ceftizoxime

目的优化头孢唑肟酸合成条件。方法考察四氢呋喃,乙酸乙酯,二氯甲烷,N,N-二甲基乙酰胺四种溶剂对7-氨基-3-去甲基-3-头孢烷酸(7-ANCA)与2-(2-氨基-4-噻唑基-2-甲氧亚胺乙酸苯并噻唑硫酯(AE活性酯)合成头孢唑肟酸收率的影响。结果确立了较优合成工艺条件:以乙酸乙酯为溶剂,n(7-ANCA)∶n(AE活酯)∶n(三乙胺)=1︰1.2︰2时,产品收率91.8%,纯度99.85%(HPLC),产品质量符合药典标准。结论此方法简捷、易于产业化。

Objective To optimize the manufacturing process of ceftizoxime. Methods It was appreciated that the preparation of ceftizoxime by reaction of 7-amino-3-nor-3-cephem-4-carboxylic acid （7-ANCA） with 2-（2- aminothiazol-4-thiazolyl）-2-[[（Z）-methoxy]imino]acetic acid S-mercapto ben-zothiazolylester （activated ester） in different kind solvents, such as tetrahydrofuran, ethyl acetate, dichlor-omethane, N,N-dimethylacetamide. Results The optimum conditions were as follows： while using ethyl acetate as solvent, the molar ratio of 7-ANCA to activated ester and triethylamine was1：1.2：2, the yield of ceftizoxime was about 91.8% and purity was 99.85%（HPLC）. The quality of product conforms to the Chinese Pharmcopoeia standards. Conclusions This method was simple, rapid and easy to scale up industrially.