氨噻肟酸乙酯的合成

Synthesis of Ethyl(Z)-2-Methoxyimino-2-(2-aminothiazole-4-yl) acetate

本文对采用乙酰乙酸乙酯法制备氨噻肟酸乙酯路线中的卤代反应进行优化,以1,3-二氯-5,5-二甲基海因和1,3-二溴-5,5-二甲基海因作卤代试剂,对甲苯磺酸作催化剂的条件下,制备得到相应的4-氯/溴-2-甲氧亚胺基乙酰乙酸乙酯卤代产物。该卤代产物进一步与硫脲进行环合反应得到目标产物(Z)-2-(2-氨基-4-噻唑)-2-甲氧基亚胺基乙酸乙酯(即氨噻肟酸乙酯)。该合成路线具有成本低、绿色环保和易于工业化的优点。

In this paper,we reported a new way to realize the halogenation reaction in the preparation of ethyl(Z)-2-methoxyimino-2-(2-aminothiazole-4-yl)acetate with ethyl acetoacetate method.We took the 1,3-dichloro-5,5-dimethylhydantoin and 1,3-dibromo-5,5-dimethylhydantoin as the halogenation reagents and p-toluenesulfonic acid as the catalyst,to prepare the corresponding ethyl 4-chloro/bromo-2-methoxyimino-3-oxobutanoate product.Then,the product was further subjected to a cyclization reaction with thiourea to obtain the objective product ethyl(Z)-2-methoxyimino-2-(2-aminothiazole-4-yl)acetate.The synthetic route has the advantages of low cost,environmentally friendly and ease of industrialization.