2-(5-氨基-1,2,4-噻二唑-3-基)-2-(Z)-甲氧亚胺基乙酸苯并噻唑硫酯的合成工艺改进

以氨噻二唑肟乙酸(Ⅰ)与二硫化二苯并噻唑(Ⅱ)为原料,三苯基膦为还原剂,制备了第四代头孢菌素中间体氨噻二唑肟乙酸苯并噻唑硫酯(Ⅲ)。研究了溶剂、温度及原料投料比对该产物收率及质量的影响。结果表明,当以1,2-二氯乙烷作溶剂,n(Ⅰ)∶n(Ⅱ)∶n(三苯基膦)=1.0∶1.0∶1.0,反应在室温进行时,收率可达98.1%(基于Ⅰ计算),HPLC测定w(Ⅲ)=98.7%。在工艺改进的条件下,反应时间缩短,生产条件简化,收率得到较大提高,成本降低。

Improvement in the Synthesis of 2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-(Z)-methoxyiminoacetic Acid 2-Benzothiazolyl Thioester

2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-(Z)-methoxyiminoacetic acid 2-benzothiazolyl thioester,an important intermediate of the fourth generation cephalosporins,was efficiently synthesized by reacting 2-(5amino-1,2,4-thiadiazol-3-yl)-2-(Z)-methoxyiminoacetic acid(Ⅰ) with 2,2′-dibenzothiazole disulfide(Ⅱ) in the presence of triphenylphosphine.An improved procedure suitable for industrial production was established.Using 1,2dichloroethane as solvent,triphenylphosphine as reducer and triethylamine as catalyst,n(Ⅰ)∶n(Ⅱ)∶n(triphenylphosphine)=1.0∶1.0∶1.0,the product was obtained at room temperature with a yield of 98.1%.The purity of the product without further purification is 98.7% by HPLC method.This procedure was a suitable alternative to the traditional processes due to easy handling,high yield and low cost.