4-Methylpyrazole → 2,2,2-Trifluoro-1-[5-methoxy-2-(4-methyl-pyrazol-1-yl)-phenyl]-ethanol

HRID 1620845Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[CH:10]([OH:15])[C:11]([F:14])([F:13])[F:12].[CH3:16][C:17]1[CH:18]=[N:19][NH:20][CH:21]=1.C([O-])([O-])=O.[K+].[K+].CN[C@@H]1CCCC[C@H]1NC>C(OCC)(=O)C.[Cu]I.C1(C)C=CC=CC=1>[F:12][C:11]([F:14])([F:13])[CH:10]([C:3]1[CH:4]=[C:5]([O:8][CH3:9])[CH:6]=[CH:7][C:2]=1[N:19]1[CH:18]=[C:17]([CH3:16])[CH:21]=[N:20]1)[OH:15]

Participants

Conditions

Temperature: 130 °C

Procedure

1-(2-Bromo-5-methoxy-phenyl)-2,2,2-trifluoro-ethanol (0.570 g, 2.0 mmol), 4-methyl pyrazole (0.164 g, 2.0 mmol), CuI (0.057 g, 0.3 mmol), K2CO3 (0.580g, 4.2 mmol), (1R,2R)-N,N′-dimethyl-cyclohexane-1,2-diamine (0.071 g, 0.5 mmol) and toluene (10 ml) were combined in a 20 ml pressure tube, and the mixture was heated at 130° C. (oil bath temperature) for 12 h. The mixture was diluted with ethyl acetate and washed with H2O (2×20 ml), brine, and dried over sodium sulfate. Removal of solvent gave a crude product, which was purified by ISCO column chromatography using 5-10% ethyl acetate in hexane as solvent to afford 2,2,2-trifluoro-1-[5-methoxy-2-(4-methyl-pyrazol-1-yl)-phenyl]-ethanol (90 mg).

Workup

washwashed with H2O (2×20 ml), brine
dry with materialdried over sodium sulfate
customRemoval of solvent
customgave a crude product, which
customwas purified by ISCO column chromatography

Sources & evidence

ORD record: ord-5873de1191954a7ba8fb99a472a2745d
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08772482B2

Reaction notes

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