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    • 60. 发明申请
    • AN IMPROVED PROCESS FOR PREPARATION OF LEFLUNOMIDE
    • 改进制备LEFLUNOMIDE的改进方法
    • WO2007086076A3
    • 2009-04-30
    • PCT/IN2006000359
    • 2006-09-12
    • UNICHEM LAB LTDRAMAKRISHNAN ARULGOBIND KAPKOTINEERAJ KUMARDNYANESHWAR SHINGARE
    • RAMAKRISHNAN ARULGOBIND KAPKOTINEERAJ KUMARDNYANESHWAR SHINGARE
    • C07D261/18
    • C07D261/18
    • This invention describes a process for the preparation of N-(4-trifluoromethyl)-5-methylisoxazole-4-carboxamide commonly known as leflunomide comprising : (a) reacting ethylaceto acetate, triethylorthoformate, and acetic anhydride with simultaneous distillation to form ethyl ethoxymethyleneacetoacetic ester; (b) reacting the ethyl ethoxymethyleneacetoacetic ester with aqueous hydroxylamine without using any external base and without any distillation to form ethyl-5-methylisoxazole-4-carboxylate; (c) reacting the ethyl-5-methylisoxazole-4-carboxylate with strong acid to form -5-methylisoxazole-4-carboxylic acid; (d) 5-methylisoxazole-4-carboxylic acid is reacted with thionyl chloride in presence of N, N-Dimethylformamide and equimolar of 4-trifluoromethylaniline without any external base to obtain highly pure Leflunomide.
    • 本发明描述了制备通常称为来氟米特的N-(4-三氟甲基)-5-甲基异恶唑-4-甲酰胺的方法,其包括:(a)同时蒸馏乙基乙酸乙酯,原甲酸三乙酯和乙酸酐,形成乙基乙氧基亚甲基乙酰乙酸酯 ; (b)使乙基乙氧基亚甲基乙酰乙酸酯与羟胺水溶液反应而不使用任何外部碱,不进行任何蒸馏以形成乙基-5-甲基异恶唑-4-羧酸乙酯; (c)使5-甲基异恶唑-4-羧酸乙酯与强酸反应形成-5-甲基异恶唑-4-羧酸; (d)将5-甲基异恶唑-4-羧酸与N,N-二甲基甲酰胺和等摩尔的4-三氟甲基苯胺在没有任何外部碱的存在下与亚硫酰氯反应,得到高纯度的来氟米特。