4'-Bromo-2,2,2-trifluoroacetophenone → 2-(4-Bromophenyl)-1,1,1-trifluoropropan-2-ol

Participants

Reaction Conditions

Reaction Steps

4′-Bromo-2,2,2-trifluoroacetophenone (1.80 mL, 11.9 mmol) was stirred in THF (60 mL) at 0° C. under an argon atmosphere. Methylmagnesium bromide (19.8 mL, 59.3 mmol) was added and the reaction mixture was stirred at 0° C. for 1 hour and then allowed to warm to ambient temperature overnight. The reaction was quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was purified by MPLC on silica gel (using a gradient elution of 0-25% EtOAc/hexanes). Desired fractions were identified, combined, and concentrated in vacuo to afford a racemic mixture of the title compounds. The racemic residue was resolved by Chiral SFC purification (Chiral Technology AZ-H 2.1×25 cm, 5 uM column, eluted with 5% methanol).

Provenance & Evidence