4-Propylcyclohexanone → 1-(4-Bromo-2-fluorophenyl)-4-propylcyclohexanol

HRID 718492Notes

Reaction equation

[Li]CCCC.[Br:6][C:7]1[CH:12]=[CH:11][C:10](I)=[C:9]([F:14])[CH:8]=1.[CH2:15]([CH:18]1[CH2:23][CH2:22][C:21](=[O:24])[CH2:20][CH2:19]1)[CH2:16][CH3:17]>C1COCC1>[Br:6][C:7]1[CH:12]=[CH:11][C:10]([C:21]2([OH:24])[CH2:22][CH2:23][CH:18]([CH2:15][CH2:16][CH3:17])[CH2:19][CH2:20]2)=[C:9]([F:14])[CH:8]=1

Participants

Conditions

Temperature: -70 °C

Procedure

Under a nitrogen atmosphere, n-BuLi (108.0 mL, 174.0 mmol) was slowly added dropwise, at −70° C. or lower, to a THF (300 mL) solution of 4-bromo-2-fluoro-1-iodobenzene (67) (50.0 g, 166.0 mmol). The reaction mixture was agitated at −70° C. or lower for 1 hour, and then 4-propylcyclohexanone (66) (24.5 g, 174.0 mmol) was slowly added dropwise thereto. The reaction mixture was returned to room temperature, and then quenched with 200 mL of 1N hydrochloric acid aqueous solution, and extracted with 100 mL of toluene three times. Combined organic layers were washed with a saturated aqueous solution of sodium hydrogencarbonate, water and saturated brine, and then dried over magnesium sulfate, and a solvent was distilled off by an evaporator. The residue was purified by silica gel column chromatography, and thus 1-(4-bromo-2-fluorophenyl)-4-propylcyclohexanol (68) (42.0 g, yield 80.2%) was obtained.

Workup

customwas returned to room temperature
customquenched with 200 mL of 1N hydrochloric acid aqueous solution
extractionextracted with 100 mL of toluene three times
washCombined organic layers were washed with a saturated aqueous solution of sodium hydrogencarbonate, water and saturated brine
dry with materialdried over magnesium sulfate
distillationa solvent was distilled off by an evaporator
customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record: ord-0add0333bdc349d8ab777f13d82e21bb
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09193908B2

Reaction notes

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