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

Temperature

0 °C

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).

1. temperatureto warm to ambient temperature overnight
2. customThe reaction was quenched with saturated aqueous ammonium chloride
3. extractionextracted with ethyl acetate
4. washThe organic layer was washed with brine
5. dry with materialdried over anhydrous MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by MPLC on silica gel (
9. washa gradient elution of 0-25% EtOAc/hexanes)
10. concentrationconcentrated in vacuo
11. customto afford
12. customThe racemic residue was resolved by Chiral SFC purification (Chiral Technology AZ-H 2.1×25 cm, 5 uM column, eluted with 5% methanol)

ORD record

ord-e7737cb7da75455ba5d31ba3b84e5b68

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08962608B2