FIELD: chemical or physical processes.
SUBSTANCE: invention relates to a method of producing (4-trifluoromethylphenyl)-amide (Z)-2-cyano-3-hydroxybut-2-enoic acid of formula I (teriflunomide). Method includes steps a)–d). Step a) converts 5-methylisoxazole-4-carboxylic acid of formula V into 5-methylisoxazole-4-carbonyl chloride of formula IV using a chlorinating agent. Step b) comprises reacting a compound of formula IV with 4-(trifluoromethyl)aniline of formula III in a two-phase medium in the presence of an inorganic base to obtain N-(4'-trifluoromethylphenyl)-5-methylisoxazole-4-carboxamide of formula II. At step c) reacting compound of formula II with aqueous sodium hydroxide in a mixture of solvents to obtain (4-trifluoromethylphenyl)-amide (Z)-2-cyano-3-hydroxybut-2-enoic acid of formula I, wherein N-(4'-trifluoromethylphenyl)-5-methylisoxazole-4-carboxamide of formula II is not isolated. At step d) it is possible to purify the compound of formula I from a mixture of solvents to obtain a pure crystalline compound of formula I—(4-trifluoromethylphenyl)-amide (Z)-2-cyano-3-hydroxybut-2-enoic acid. Invention also relates to versions of said method.
EFFECT: disclosed method reduces the number of steps and enables to obtain a product with higher output and degree of purity.
19 cl, 7 dwg, 1 tbl, 10 ex
