(Trifluoromethyl)trimethylsilane → 1-(5-bromo-2-fluorophenyl)-2,2,2-trifluoroethan-1-ol

A solution of 5-bromo-2-fluorobenzaldehyde (5.05 g, 24.9 mmol) in THF (200 mL) was cooled in a wet ice bath and treated dropwise with TMS-CF3 over five minutes. After stirring for 10 minutes, a solution of tetrabutylammonium fluoride (TBAF) in THF (1.0 mL, 1.0M) was added dropwise over 5 minutes. After stirring for 10 minutes, the ice bath was removed and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was treated with 1N HCl (50 mL) and allowed to stir for 2 hours. The mixture was diluted with 1N HCl (50 mL) and extracted with EtOAc (200 mL). The organic layer was washed with saturated aqueous NaHCO3 (2×50 mL) and brine (50 mL), dried over Na2SO4, filtered and concentrated. Purification by flash column chromatography (silica gel, hexanes/EtOAc, 100:0 to 95:5) provided the title compound (3.28 g, 48%) as a colorless liquid. 1H NMR (500 MHz, CDCl3) δ 7.76 (dd, J=6.0, 2.0 Hz, 1H), 7.50 (ddd, J=8.5, 4.5, 2.5 Hz, 1H), 7.00 (overlapping dd, J=9.0, 9.0 Hz, 1H), 5.39 (overlapping dq, J=6.0, 6.0 Hz, 1H), 2.86 (d, J=5.5 Hz, 1H).

1. stirringAfter stirring for 10 minutes
2. customthe ice bath was removed
3. stirringthe reaction mixture was stirred at room temperature for 16 hours
4. additionThe reaction mixture was treated with 1N HCl (50 mL)
5. stirringto stir for 2 hours
6. additionThe mixture was diluted with 1N HCl (50 mL)
7. extractionextracted with EtOAc (200 mL)
8. washThe organic layer was washed with saturated aqueous NaHCO3 (2×50 mL) and brine (50 mL)
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated
12. customPurification by flash column chromatography (silica gel, hexanes/EtOAc, 100:0 to 95:5)

ORD record

ord-ec07be10ca964b169a72a3960ee90ddb

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08268868B2