4-Aminophenol → 4-((2-(Trifluoromethyl)pyrimidin-4-yl)oxy)aniline

HRID 729985Notes

Reaction equation

HRID 729985 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].Cl[C:16]1[CH:21]=[CH:20][N:19]=[C:18]([C:22]([F:25])([F:24])[F:23])[N:17]=1.O>CN(C=O)C>[F:23][C:22]([F:25])([F:24])[C:18]1[N:19]=[C:20]([O:8][C:5]2[CH:6]=[CH:7][C:2]([NH2:1])=[CH:3][CH:4]=2)[CH:21]=[CH:16][N:17]=1

Participants

6

Reactant 4

HCID 4034-AminophenolHCID 962WaterHCID 152943694-Chloro-2-(trifluoromethyl)pyrimidineHCID 23665647Potassium tert-butoxide

Product 1

HCID 288753264-((2-(Trifluoromethyl)pyrimidin-4-yl)oxy)anilineYield 63%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 4-aminophenol (1.64 g, 15 mmol) in DMF (40 mL) was added potassium tert-butoxide (1.69 g, 15 mmol) and the resulting mixture was stirred at room temp for 15 min. 4-chloro-2-(trifluoromethyl)pyrimidine in DMF (10 mL) was then added and the resulting mixture was stirred at room temp for 16 h. Water was then added and the mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate and concentrated in vacuo. The crude was purified using Biotage flash 40M (2:1, Hexane, Ethyl acetate) to afford 4-{[2-(trifluoromethyl)pyrimidin-4-yl]oxy}aniline (2.2 g, 63%). 1H NMR (DMSO-d6) δ 8.78 (d, 1H), 7.16 (d, 1H), 6.90 (d, 2H), 6.60 (d, 2H), 5.17 (brs, 2H); MS ES 256 (M+H)+, calcd 256, RT=2.42 min.

Workup

  1. stirringthe resulting mixture was stirred at room temp for 16 h
  2. extractionthe mixture was extracted with ethyl acetate
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe crude was purified

Sources & evidence

ORD record
ord-93daf2ec339f49dd8c3730d845975176
Source dataset
uspto-grants-2009_09
Patent number
US07582646B2

Reaction notes

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