Azobisisobutyronitrile → 1-(Bromomethyl)-2-(difluoromethyl)benzene

To a solution of 1-(difluoromethyl)-2-methylbenzene (2.90 g, 20.4 mmol) in carbon tetrachloride (50 mL) was added N-bromosuccinimide (3.63 g, 20.4 mmol) and 2,2′-azobis(2-methylpropionitrile) (0.167 g, 1.02 mmol). The mixture was heated at reflux for 16 h. Further 2,2′-azobis(2-methylpropionitrile) (0.167 g, 1.02 mmol) was added, the mixture was heated at reflux for 4 h, allowed to cool to ambient temperature, diluted with dichloromethane (175 mL) and washed with water (2×175 mL) and saturated sodium bicarbonate (150 mL). The organic phase was dried over sodium sulfate, filtered, and concentrated in vacuo. The resultant residue was purified by column chromatography and eluted with a 0% to 10% gradient of ethyl acetate in dichloromethane to afford 1-(bromomethyl)-2-(difluoromethyl)benzene as a yellow solid: 1H NMR (300 MHz, CDCl3) δ 7.58-7.56 (m, 1H), 7.43-7.37 (m, 3H), 6.95 (t, JH-F=55.2 Hz, 1H), 4.59 (s, 2H).

1. temperatureThe mixture was heated
2. temperatureat reflux for 16 h
3. temperaturethe mixture was heated
4. temperatureat reflux for 4 h
5. washwashed with water (2×175 mL) and saturated sodium bicarbonate (150 mL)
6. dry with materialThe organic phase was dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe resultant residue was purified by column chromatography
10. washeluted with a 0% to 10% gradient of ethyl acetate in dichloromethane

ORD record

ord-aa9f07b4c96141668ec886d2e0733b05

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08916580B2