摘要
在溶剂碳酸二甲酯(一种低毒、环保性能优异的化工原料)中,7-氨基头孢烷酸(7-ACA)与1-(2-二甲基氨基乙基)-1H-5-巯基四氮唑(MTZ)缩合生成头孢替安三位中间体7-ACMT,水解后不经分离,7-AC-MT直接与.氨基噻唑乙酰氯盐酸盐(七位侧链)缩合生成头孢替安.采用一勺烩工艺合成目标产物头孢替安,简化工艺过程;优化溶剂比例和工艺条件,减少精制过程,减少有机溶媒的使用种类和数量,降低工艺成本,利于工艺环保操作控制.结果表明,工艺中使用的有机溶媒易降解毒性小,利于工艺回收利用.产品质量分数可提高到99.0％,产品色级可控制在2#以下,未知杂质质量分数可控在0.15％以下,适合产业化生产应用.
Abstract
The 3-position intermediate of cefotiam(7-ACMT)was synthesized from 7-amino-cephalosporanic acid(7-ACA)and 1-(2-dimethylaminoethyl)-1H-5-mercaptotetrazole(MTZ)in dimethyl carbonate,a green environmentally friendly solvent.After hydrolysis,7-ACMT was directly condensed with aminothiazole acetyl chloride hydrochloride(7-position side chain)to produce cefotiam without separation.A one-pot process was adopted to obtain a simplified technological process.The solvent ratio and process conditions were optimized to simplify the process.The types and quantity of organic solvents were reduced for cost reduction.Thus,a more environment friendly process is obtained.The results showed that the organic solvent used in this method is easy to degrade and less toxic,which is beneficial to the recovery and utilization of the process.The product quality score is 99.0％,the color grade of product was controlled below 2#,and the quality score of unknown impurity was controlled below 0.15％to meet the quality requirements of domestic and foreign customers and to be more suitable for industrial production applications.
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