活性硫酯法制备头孢地尼新工艺  

A new method of the synthesis of cefdinir by BTATA

作　　者：张静[1] 范继业[1] 刘清涛[1] 高冬婷 马丽锋[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 [2]石药集团中诺药业,石家庄050000

出　　处：《中国抗生素杂志》2015年第9期667-671,共5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。方法以7-氨基-3-乙烯基头孢烷酸(7-AVCA)为起始原料,在三乙胺的N,N-二甲基乙酰胺(DMAc)溶液中,与三苯甲基活性硫酯(BTATA)缩合得到三苯地尼甲基磺酸盐3DMAc溶剂化物;在乙腈中,甲酸和硫酸作用下脱除三苯甲基保护基,形成头孢地尼盐酸盐,再在水溶液中精制得到头孢地尼。结果总收率为72.5%(以7-AVCA计),高效液相色谱测得纯度>99%。结论对合成工艺进行研究和改进,达到药典标准。Objective To improve production process of the cefdinir cost-cut, simplify operation procedure and improve yield. Methods Trityl cefdinir methanesulfonic acid salt of DMAc solution was obtained by condensation reaction from 7-amino-3-vinyl-3-cephem-4-carboxylic acid （7-AVCA） and BTATA in N,N-dimethylacetamide in the presence of triethylamine. The trityl protective product obtained was cleavaged with the mixture of formic acid and sulfuric acid in acetonitrile to give sulfuric acid salt of cefdinir. Cefdinir was obtained by purification of sulfuric acid salt of cefdinir with sodium bicarbonate in water. Results The total yield was 72.5% and the purity of the product was higher than 99%（HPLC）. Conclusion The product quality accorded with the standard of Chinese pharmacopoeia.

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]