Benzyl Alcohol → 2-(Benzyloxy)-3-bromobenzonitrile

Temperature

0 °C

To a flask containing sodium hydride (1.44 g, 60.0 mmol) suspended in DMF (60 mL, 800 mmol) at 0° C. was added benzyl alcohol (6.21 mL, 60.0 mmol) over 5 min. The reaction mixture was stirred at 0° C. for 30 min and then 3-bromo-2-fluorobenzonitrile (10.0 g, 50.0 mmol) in DMF (20 mL) was added. The reaction mixture was warmed to room temperature and stirred at at 80° C. for 2 h, cooled to room temperature, and extracted with ethyl acetate (150 mL) and water (150 mL) The organic layer was washed with water (150 mL) and brine (150 mL), collected, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was suspended with ethyl acetate: hexanes (1:3; 50 mL). The resulting suspension was stirred vigorously for 1 h, filtered, and dried. The mother liquor was concentrated and recrystallized. The crystals were combined and dried under vacuum to give the title compound (10.3 g). 1H NMR (DMSO-d6, 300 MHz) δ (ppm): 8.04 (dd, J=1.6, 8.2 Hz, 1H), 7.87 (dd, J=1.6, 7.6 Hz, 1H), 7.56-7.51 (m, 2H), 7.47-7.37 (m, 3H), 7.29 (t, J=7.9 Hz, 1H), 5.20 (s, 1H).

1. temperatureThe reaction mixture was warmed to room temperature
2. stirringstirred at at 80° C. for 2 h
3. temperaturecooled to room temperature
4. extractionextracted with ethyl acetate (150 mL) and water (150 mL) The organic layer
5. washwas washed with water (150 mL) and brine (150 mL)
6. customcollected
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. stirringThe resulting suspension was stirred vigorously for 1 h
11. filtrationfiltered
12. customdried
13. concentrationThe mother liquor was concentrated
14. customrecrystallized
15. customdried under vacuum

ORD record

ord-edb73d6e46bc4bd8a492914a71499da7

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08802698B2