(Z)-2 - [(5-氨基-[1,2,4]噻二唑-3-基)-羧基-亚甲基氨基氧基]-2-甲基-丙酸叔丁酯的制备方法

摘要：本文探索头孢洛扎中间体的制备方法。首先将起始物料2-(5-氨基-1,2,4-噻二唑-3-基)-2-甲氧亚氨基乙酸与甲醇进行反应得到化合物1，然后化合物1与盐酸羟胺反应得到化合物2，其次化合物2与α-溴代异丁酸叔丁酯进行缩合反应得到化合物3，最后通过水解反应制备(Z)-2-[(5-氨基-[1,2,4]噻二唑-3-基)-羧基-亚甲基氨基氧基]-2-甲基-丙酸叔丁酯(简称TATD)。该产品的纯度与总摩尔收率分别为99.1%、66.1%，且反应原料易得，适合工业化规模生产。

The method for preparing (Z)-2-[(5-Amino-[1,2,4]thiadiazol-3-yl)-carboxymethyleneaminooxy]-2-methyl-propionic acid tert-butyl ester

Abstract This paper explored the method for preparing ceftolozane intermediate. First, the starting material2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(methoxyimino)acetic acid was reacted with methanol to obtain compound 1.Subsequently, compound 1 was combined with the hydroxylamine hydrochloride to synthesize compound 2, andcompound 2 was reacted with the t-butyl 2-bromo isobutyrate to obtain compound 3. Finally, (Z)-2- [(5-amino-[1,2,4]thiadiazol-3-yl) -carboxy-methylene aminooxy]-2-methyl-propionate tert-butyl ester (TATD) was prepared via thehydrolysis reaction. The purity and total molar yield of the product were 99.1% and 66.1%, respectively. Furthermore, theraw materials of this process were easy to obtain. The process could thus easily be scaled up to an industrial process.