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

Participants

Reaction Conditions

Reaction Steps

4′-Bromo-2,2,2-trifluoroacetophenone (3.00 mL, 19.8 mmol) was dissolved in MeOH (66 mL) and cooled to 0° C. Sodium borohydride (0.748 g, 19.8 mmol) was added, and the reaction mixture was allowed to warm to ambient temperature where it was maintained for an additional 3 hours. The reaction mixture was quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous MgSO4, filtered, concentrated in vacuo and the crude residue was purified using MPLC on silica gel (eluting with 5% ethyl acetate in hexanes) to afford a racemic mixture of the title compound. The mixture was resolved to the constituent enantiomers by Chiral SFC purification (Chiral Technology OJ-H 2.1×25 cm, 5 uM; mobile phase: 5% isopropyl alcohol/CO2) to afford the title compounds as single enantiomers. Intermediate #10-1: First enantiomer to elute; (R or S)-1-(4-Bromophenyl)-2,2,2-trifluoroethanol; 1H NMR (500 MHz, CDCl3) δ 7.56-7.54 (d, 2H), 7.37-7.35 (d, 2H), 5.03-4.98 (m, 1H), 2.79 (bs, 1H). Intermediate #10-2: Second enantiomer to elute; (R or S)-1-(4-Bromophenyl)-2,2,2-trifluoroethanol; 1H NMR (500 MHz, CDCl3) δ 7.56-7.54 (d, 2H), 7.37-7.35 (d, 2H), 5.03-4.98 (m, 1H), 2.79 (bs, 1H).

Provenance & Evidence