Cesium carbonate → 3-[4-(Trifluoromethyl)phenoxy]aniline

HRID 990444Notes

Reaction equation

[NH2:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.Br[C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(N(C)C)=O.O>[F:17][C:16]([F:19])([F:18])[C:13]1[CH:14]=[CH:15][C:10]([O:8][C:4]2[CH:3]=[C:2]([CH:7]=[CH:6][CH:5]=2)[NH2:1])=[CH:11][CH:12]=1

Participants

Conditions

Temperature: 85 °C

Procedure

EX-656A) 3-Aminophenol (5.0 g, 45.8 mmol) and 4-bromo-α,α,α-trifluorotoluene (14.0 g, 62.2 mmol) were dissolved in anhydrous dimethylacetamide (20 mL), then anhydrous cesium carbonate (30 g, 92.3 mmol) and copper triflate benzene complex (200 mg) were added. The mixture was stirred and heated to 85° C. using a reflux condenser under an argon atmosphere. After 16 h, the mixture was diluted with water (120 mL), and the aqueous layer was extracted with diethyl ether (4×60 mL). The combined ether layers were washed with 3% HCl, 5% NaOH and water, then dried over anhydrous MgSO4. The ether was removed in vacua, and the recovered oil purified by flash column chromatography on silica gel eluting with ethyl acetate in hexane (1:8) to give 6.8 g (59%) of the desired 3-(4-trifluoromethylphenoxy)aniline product as a yellow oil, which solidified to a yellow powder, 98% pure by HPLC analysis. HRMS calcd. for C13H10 F3NO: 254.0792 [M+H]+, found: 254.0798.

Workup

extractionthe aqueous layer was extracted with diethyl ether (4×60 mL)
washThe combined ether layers were washed with 3% HCl, 5% NaOH and water
dry with materialdried over anhydrous MgSO4
customThe ether was removed in vacua
customthe recovered oil purified by flash column chromatography on silica gel eluting with ethyl acetate in hexane (1:8)

Sources & evidence

ORD record: ord-9f81f4ff34054e60878d2253585dd371
Source dataset: uspto-grants-2002_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06458803B1

Reaction notes

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