来氟米特的合成

Synthesis of Leflunomide

以价廉易得的乙酰乙酸乙酯为起始原料 ,缩合、环合后中间产物 3不分离 ,水解得到 6 8%的 5 -甲基 - 4-异唑甲酸 ,经氯化、纯化后与对三氟甲基苯胺反应得到来氟米特 ,两步收率 6 0 .8% ,总收率 41%。操作简便 。

Leflunomide, a new drug for treating rheumatoid arthritis, was synthesized from ethyl acetoacetate and triethyl orthoformate by condensation, cyclization, hydrolysis and chlorination to obtain 5 methyl 4 isoxazolecarboxylic acid chloride which reacted with 4 trifluoromethylaniline to give the desired product in an overall yield of 41%.