4-(Trifluoromethyl)aniline → Leflunomide

Participants

Reaction Conditions

Reaction Steps

4-Trifluoromethylaniline (5.75 g, 35.7 mm) was suspended in a solution of NaHCO3 (3.16 g, 37.6 mm) in water (30 ml). The suspension was warmed to 50° C. and then rapid stirring was begun. 5-Methylisoxazole-4-carboxylic acid chloride prepared by the procedure of Example 1 (5 g, 34.4 mm) was added dropwise to the rapidly stirred suspension over 20 min. After cessation of the addition, the mixture was stirred for another 2 h. The mixture was then allowed to cool to ambient temperature and leflunomide was isolated as a white powder by filtration. Drying at 60° C. gave leflunomide (8.2 g, 88%) in 96% purity by HPLC analysis.

Provenance & Evidence