4-Bromo-2-fluorobenzaldehyde → 1-(4-Bromo-2-fluorophenyl)-2,2,2-trifluoroethanol

Temperature

0 °C

To a 0° C. solution of 4-bromo-2-fluorobenzaldehyde (1.00 g, 4.93 mmol) in tetrahydrofuran (50 mL) was added trimethylsilyl trifluoromethane (0.77 mL, 4.9 mmol) dropwise over 5 minutes. The reaction was stirred at 0° C. for 10 minutes. Then tetrabutylammonium fluoride (0.49 mL, 0.49 mmol, 1 M in tetrahydrofuran) was slowly added and the reaction was allowed to gradually warm to room temperature and stir for 3 days. The reaction was concentrated and the residue was taken up in dichloromethane. The solution was washed once with 1 N aqueous hydrochloric acid and once with brine. The organics were dried over magnesium sulfate, filtered, and concentrated. Purification by column chromatography (0-50% ethyl acetate/heptanes) gave the title compound (1.0 g, 75%) as a clear oil. 1H NMR (400 MHz, CDCl3, δ): 7.48 (d, J=7.61 Hz, 1H), 7.39 (d, J=1.76 Hz, 1H), 7.29 (dd, J=9.56, 1.95 Hz, 1H), 5.33-5.40 (m, 1H), 2.70 (d, J=5.46 Hz, 1H).

1. temperatureto gradually warm to room temperature
2. stirringstir for 3 days
3. concentrationThe reaction was concentrated
4. washThe solution was washed once with 1 N aqueous hydrochloric acid and once with brine
5. dry with materialThe organics were dried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customPurification by column chromatography (0-50% ethyl acetate/heptanes)

ORD record

ord-c4066fd38df249e1bc4e10ba2c573fda

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08993586B2