2-(2-氨基噻唑-4-基)-2-(Z)-甲氧亚胺基乙酸苯并噻唑硫酯合成工艺的改进

对2-(2-氨基噻唑-4-基)-2-(Z)-甲氧亚胺基乙酸苯并噻唑硫酯(Ⅶ)的合成工艺进行了改进研究,即以价格相对便宜的乙酰乙酸甲酯代替目前工业上普遍采用的乙酰乙酸乙酯为原料,通过亚硝化、醚化、溴化、环合、水解、脱水、硫酯化7步反应制备Ⅶ,总收率31.6%(摩尔)。水解反应采用氢氧化钠-甲醇-水体系代替氢氧化钠-水体系;环合反应采用N,N-二甲基苯胺代替乙酸钠;溶剂用二氯甲烷代替乙醇-水,使环合物颜色较浅;硫酯化反应做了重大改进,采用廉价的亚磷酸三乙酯(2万元/t)代替昂贵易水解的三苯基磷(12万元/t)。基于工艺改进,Ⅶ的成本由20万元/t降到13万元/t。所得活性酯试用于头孢噻肟钠、头孢地嗪钠的合成,产品合格。

An Improved Procedure for the Preparation of 2-(2-Aminothiazol-4-yl)-2-(Z)-methoxyiminoacetic Acid S-Benzthiazolyl Thioester

2-(2-Aminothiazol-4-yl)-2-(Z)-methoxyiminoacetic acid S-benzthiazolyl thioester was synthesized from methyl acetoacetate through nitrosation,methylation,bromination,cyclization,hydrolysis,dehydration and thioesterification in overall yield of 31.6%.Each step of the synthesis process was improved.Especially,in the cyclization reaction,N,N-dimethylaniline was used as base in place of sodium acetate and CH_2Cl_2 as solvent instead of C_2H_5OH-H_2O.Triethyl phosphite was substituted for triphenylphosphine in the thioesterification reaction.By virtue of these improvements,the procedure was simplified and the production cost was reduced by 35%.