Boron tribromide → 4-Chloro-2-(1,1,1-trifluoro-2-methylpropan-2-yl)phenol

Temperature

-78 °C

Boron tribromide (1 M in dichloromethane, 16.8 mL, 16.8 mmol) was added drop-wise over 10 minutes to a −78° C. solution of 4-chloro-1-methoxy-2-(1,1,1-trifluoro-2-methylpropan-2-yl)benzene (C47) (850 mg, 3.36 mmol) in dichloromethane (10 mL). After stirring at −78° C. for 30 minutes, the reaction mixture was heated to 40° C. and held at that temperature for 24 hours. The reaction mixture was then cooled to −78° C. and quenched with saturated aqueous sodium bicarbonate solution (10 mL). The pH was adjusted to approximately 5 with aqueous hydrochloric acid, and the mixture was extracted with dichloromethane (3×50 mL). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. Purification using silica gel chromatography (Gradient: 0% to 20% ethyl acetate in heptane) afforded the product as a colorless oil. Yield: 515 mg, 2.16 mmol, 64%. GCMS m/z 238 (M+). 1H NMR (400 MHz, CDCl3) δ 1.67 (br s, 6H), 5.37 (br s, 1H), 6.71 (d, J=8.6 Hz, 1H), 7.14 (dd, J=8.6, 2.5 Hz, 1H), 7.33-7.36 (m, 1H).

1. temperaturethe reaction mixture was heated to 40° C.
2. waitheld at that temperature for 24 hours
3. temperatureThe reaction mixture was then cooled to −78° C.
4. customquenched with saturated aqueous sodium bicarbonate solution (10 mL)
5. extractionthe mixture was extracted with dichloromethane (3×50 mL)
6. dry with materialThe combined organic layers were dried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customPurification

ORD record

ord-e8c81e8e34214167b49cadce81a3dfb2

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09067934B2