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

Temperature

0 °C

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).

1. temperatureto warm to ambient temperature where it
2. temperaturewas maintained for an additional 3 hours
3. customThe reaction mixture was quenched with saturated aqueous ammonium chloride
4. extractionextracted with ethyl acetate
5. washThe organic layer was washed with brine
6. dry with materialdried over anhydrous MgSO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customthe crude residue was purified
10. customto afford

ORD record

ord-3b021524338240eda0f49704af49a168

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09394282B2