来氟米特的合成工艺研究

A Study on the Synthetic Technology of Leflunomide

以乙酰乙酸乙酯与原甲酸三乙酯为起始原料 ,经缩合得到相应的乙氧亚甲基衍生物 ,然后与盐酸羟胺环合形成 5 甲基异唑 4 甲酸乙酯 ,再通过水解、氯化得到酰氯 ,最后与 4 三氟甲基苯胺反应得到来氟米特 ,总收率为 32 .2 %

An improved method was developed for the synthesis of leflunomide.Thus,ethyl acetoacetate reacted with triethyl orthoformate to give the corresponding ethoxymethylene derivative,which by cyclization with hydroxylamine hydrochloride afforded 5 methylisoxazole 4 carboxylic acid ethyl ester.The hydrolysis of this ester under acidic condition yielded the free acid,which was converted into the acid chloride.Finally,this compound was condensed with 4 (trifluoromethyl)aniline to obtain leflunomide.