Ammonium Chloride → 2-Bromo-1-(4,4-difluorocyclohexyl)-4,4-dimethylpentan-3-one

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Reaction Steps

3-(4,4-Difluorocyclohexyl)propionic acid (330 mg, 1.72 mmol) obtained in step 3 was dissolved in thionyl chloride (3.0 mL), and the solution was stirred for 4 hours under heat and reflux. The solvent was then evaporated under reduced pressure. The residue was dissolved in THF (3.3 mL) under ice-cooled condition, and the mixture was stirred at room temperature for 30 minutes after adding copper chloride(I) (8.5 mg, 0.086 mmol) and tert-butyl magnesium chloride (2 mol/L-THF solution) (1.03 mL, 2.06 mmol). Under ice-cooled condition, a saturated ammonium chloride aqueous solution was added, and the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was then evaporated under reduced pressure. The residue was dissolved in ethanol (4.0 mL), and the solution was stirred for 2 hours under heat and reflux after adding tetra-n-butylammonium tribromide (910 mg, 1.89 mmol). Under ice-cooled condition, a saturated sodium hydrogen carbonate aqueous solution was added, and the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=97/3→90/10) to give 2-bromo-1-(4,4-difluorocyclohexyl)-4,4-dimethylpentan-3-one (433 mg, yield 81%).

Provenance & Evidence