4-Aminophenol → 4-{[2-(Trifluoromethyl)pyridin-4-yl]oxy}aniline

HRID 729952Notes

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+].F[C:16]1[CH:21]=[CH:20][N:19]=[C:18]([C:22]([F:25])([F:24])[F:23])[CH:17]=1>CN(C)C(=O)C>[F:23][C:22]([F:25])([F:24])[C:18]1[CH:17]=[C:16]([O:8][C:5]2[CH:6]=[CH:7][C:2]([NH2:1])=[CH:3][CH:4]=2)[CH:21]=[CH:20][N:19]=1

Participants

Conditions

Temperature: 20 °C

Procedure

A cold (−5° C.), de-gassed solution of 4-aminophenol (41.6 g, 0.38 mol) in N,N-dimethylacetamide (250 mL) was treated with potassium tert-butoxide and stirred while warming to 20° C. A solution containing 4-fluoro-2-trifluoromethylpyridine (60 g, 0.36 mol) in dimethylacetamide (150 mL) was slowly added and the mixture was stirred at 25° C. for 18 h. The reaction mixture was then concentrated in vacuo and the residue was added to vigorously stirred water (1 L). The precipitated solids were collected by suction filtration and washed with isopropanol/ether (1:1) followed by ether and hexane. The yellow tan solids were dried to afford 72.8 g (79%) of product. 1H NMR (DMSO-d6) δ 5.20 (s, 2H, —NH2), 6.62 (m, 2H), 6.86 (m, 2H), 7.04 (dd, 1H, J=5.6, 2.4 Hz), 7.24 (d, 1H, J=2.4 Hz), 8.54 (d, 1H, 5.7 Hz). MS ES 255 (M+H)+, calcd 255, RT=1.66 min.

Workup

additionwas slowly added
stirringthe mixture was stirred at 25° C. for 18 h
concentrationThe reaction mixture was then concentrated in vacuo
additionthe residue was added to vigorously stirred water (1 L)
filtrationThe precipitated solids were collected by suction filtration
washwashed with isopropanol/ether (1:1)
customThe yellow tan solids were dried

Sources & evidence

ORD record: ord-740371fac4574041835c5cd12c0bb5c7
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07582646B2

Reaction notes

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