Ammonium Chloride → 4,4,4-Trifluoro-1-(4'-(trifluoromethyl)biphenyl-4-yl)butan-1-ol

HRID 2407002Notes

Reaction equation

C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)=[CH:9][CH:8]=1.[F:23][C:24]([F:30])([F:29])[CH2:25][CH2:26][CH:27]=[O:28].[NH4+].[Cl-]>C1COCC1>[F:23][C:24]([F:30])([F:29])[CH2:25][CH2:26][CH:27]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)=[CH:9][CH:8]=1)[OH:28]

Participants

Conditions

Temperature: -78 °C

Procedure

n-Butyllithium (150 uL of a 2.5M solution in hexanes, 0.38 mmol) was added dropwise to a −78° C. solution of 4-bromo-4′-(trifluoromethyl)biphenyl (113 mg, 0.375 mmol) in 3 mL THF. The resulting solution was stirred at −78° C. 15 min. 4,4,4-trifluorobutyraldehyde (98 mg, 0.78 mmol) was added neat. The resulting colorless solution was stirred at −78° C. 20 min. 1 mL sat. aqueous NH4Cl was added, and the mixture warmed to room temperature. The reaction mixture was partitioned between Et2O and water. The organic layer was dried over MgSO4 and concentrated to give a colorless oil. The crude material was purified by silica gel chromatography to provide 4,4,4-trifluoro-1-(4′-(trifluoromethyl)biphenyl-4-yl)butan-1-ol (87 mg, 67%). 1H NMR (400 MHz, CDCl3) δ 7.64-7.71 (m, 4H), 7.57-7.62) m, 2H), 7.41-7.47 (m, 2H), 4.78-4.87 (m, 1H), 2.10-2.39 (m, 3H), 1.96-2.09 (m, 1H).

Workup

custom15 min
stirringThe resulting colorless solution was stirred at −78° C
custom20 min
temperaturethe mixture warmed to room temperature
customThe reaction mixture was partitioned between Et2O and water
dry with materialThe organic layer was dried over MgSO4
concentrationconcentrated
customto give a colorless oil
customThe crude material was purified by silica gel chromatography

Sources & evidence

ORD record: ord-8f18989db6dd44a791bfa2d7b965a3d8
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08809342B2

Reaction notes

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