乙酰基保护的活性硫酯法制备头孢地尼新工艺  

A new method of the synthesis of cefdinir by acetoxy blocking cefdinir

作　　者：张静[1] 范继业[1] 陶秀娥[1] 陈慧[1] 张滨[1] 

机构地区：[1]河北化工医药职业技术学院制药工程系,石家庄050026

出　　处：《中国抗生素杂志》2016年第4期277-279,共3页Chinese Journal of Antibiotics

基　　金：河北省科技厅2013年度计划项目(No.13272615);河北省人才工程培养经费项目(No.A201400346)

摘　　要：目的优化头孢地尼的生产工艺。方法 (Z)-2-(2-氨基噻唑-4-基)-2-乙酰氧亚氨基乙酸-2巯基苯并噻唑硫酯与7-氨基-3-乙烯基头孢烷酸(7-AVCA)在三乙胺存在下,缩合得到乙酰基地尼;无须分离,用氯化铵和碳酸钾溶液处理,脱除乙酰基保护基,得到头孢地尼粗品。用磷酸处理粗品,制得头孢地尼磷酸复合物,在水溶热中用碳酸钠中和、酸析。结果头孢地尼原料药物质的量收率达70%以上,高效液相色谱测得纯度>99%。结论产品质量达到药典标准,并简化了操作步骤提高了收率。Objective To improve the production process of the cefdinir. Methods Reaction of 2-benzothiazolyl-（Z）-2-（2-aminothiazol-4-yl）-2-acetoxyiminothioacetate with 7-amino-3-vinyl-3-cephem-4- carboxylic acid（7-AVCA） in the presence of triethylamine gave acetoxy blocking cefdinir, and then cleavaging the acetoxy group by using ammonium and potasium carbonate solution without separation. Acidation of the reaction solution to give the crude cefdinir, which was treated by phosphoric acid, gave the crystal salt of cefdinir and phosphoric acid. Cefdinir was obtained by purification of phosphoric acid salt of cefdinir with sodium bicarbonate in water. Results The total yield was over 70% and the purity of was higher than 99% （HPLC）. Conclusion The product quality accorded with the standard of Chinese Pharmacopoeia, and simplified operation procedure and improved yield

关 键 词：头孢菌素 合成工艺 侧链酸 活性硫酯 头孢地尼 

分 类 号：R978.11[医药卫生—药品]