4-(Trifluoromethyl)aniline → Leflunomide

HRID 2086373Notes

Reaction equation

HRID 2086373 reaction equation
[F:1][C:2]([F:11])([F:10])[C:3]1[CH:9]=[CH:8][C:6]([NH2:7])=[CH:5][CH:4]=1.C([O-])(O)=O.[Na+].[CH3:17][C:18]1[O:22][N:21]=[CH:20][C:19]=1[C:23](Cl)=[O:24]>O>[CH3:17][C:18]1[O:22][N:21]=[CH:20][C:19]=1[C:23]([NH:7][C:6]1[CH:5]=[CH:4][C:3]([C:2]([F:10])([F:11])[F:1])=[CH:9][CH:8]=1)=[O:24]

Participants

5

Reactant 3

HCID 99644-(Trifluoromethyl)anilineHCID 516892Sodium BicarbonateHCID 27599175-Methyl-1,2-oxazole-4-carbonyl chloride

Product 1

HCID 3899Leflunomide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

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.

Workup

  1. additionwas added dropwise to the rapidly stirred suspension over 20 min
  2. additionAfter cessation of the addition
  3. stirringthe mixture was stirred for another 2 h
  4. temperatureto cool to ambient temperature

Sources & evidence

ORD record
ord-03732ff8a01d4d7aa2ae330a7f0f7f2e
Source dataset
uspto-grants-2004_04
Patent number
US06723855B2

Reaction notes

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