Boron trifluoride etherate → 4-Bromo-2-(4-chlorobenzyl)-1-fluorobenzene

To a solution of the above (5-bromo-2-fluorophenyl)-(4-chlorophenyl)-methanol (15.0 g, 48 mmol) and triethylsilane (18.5 mL, 116 mmol) in dichloromethane (40 mL) and acetonitrile (20 mL) at 0° C. under nitrogen, was slowly added boron trifluoride diethyl etherate (22.7 mL, 181 mmol). The resulting solution was stirred for 18 hours, while slowly warming to room temperature. The reaction was cooled in an ice-water bath, quenched by slow addition of 7 M aqueous potassium hydroxide solution (30 mL) and extracted with methyl tert-butyl ether (200 mL×2). The combined organic solution was washed with water (25 mL×2), brine (25 mL×2), dried (sodium sulfate), filtered and concentrated under reduced pressure. Purification by flash column chromatography over silica gel eluting with a gradient of ethyl acetate in heptane gave 2-(4-chlorobenzyl)-4-bromo-1-fluorobenzene (5.0 g, 35% yield) as a colorless oil. 1H NMR (400 MHz, chloroform-d) delta ppm 7.33-7.22 (m, 4H), 7.13 (d, J=8.4 Hz, 2H), 6.93 (dd, J=9.2, 9.2 Hz, 1H), 3.92 (s, 2H).

1. customat 0° C.
2. temperatureThe reaction was cooled in an ice-water bath
3. customquenched by slow addition of 7 M aqueous potassium hydroxide solution (30 mL)
4. extractionextracted with methyl tert-butyl ether (200 mL×2)
5. washThe combined organic solution was washed with water (25 mL×2), brine (25 mL×2)
6. dry with materialdried (sodium sulfate)
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customPurification by flash column chromatography over silica gel eluting with a gradient of ethyl acetate in heptane

ORD record

ord-a6cd88f3b34847089ecf9aec393d74a8

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08080580B2