Boron trifluoride etherate → 4-Bromo-1-fluoro-2-(4-methoxy-benzyl)-benzene

To a well stirred solution of (5-bromo-2-fluoro-phenyl)-(4-methoxy-phenyl)-methanone (22.5 g, 72.80 mmol) and triethylsilane (27.9 mL, 20.3 g, 175.0 mmol) in dichloromethane (20 mL) and acetonitrile (60 mL) at 0° C. was added boron trifluoride etherate (32.0 mL, 36.2 g, 255.0 mmol) dropwise. Boron trifluoride etherate was added at a rate so that the internal temperature did not exceed 20° C. The reaction solution was warmed to room temperature and stirred overnight. After a total of 18 hours, a solution of potassium hydroxide (5.0 g) in water (15.0 mL) was added and the resulting mixture was stirred for 2 hours. The organic phase was separated and the aqueous phase was extracted two times with diethyl ether. The combined organic phases were washed once with aqueous 1M sodium hydroxide solution and once with brine. The organic phase was dried over sodium sulfate, filtered, and concentrated under reduced pressure. Upon addition of ethanol to the resulting residue a white solid formed. The solid was collected and dried under high vacuum to afford 4-bromo-1-fluoro-2-(4-methoxy-benzyl)-benzene (20.1 g, 93% yield) as a white solid.

1. customdid not exceed 20° C
2. stirringthe resulting mixture was stirred for 2 hours
3. customThe organic phase was separated
4. extractionthe aqueous phase was extracted two times with diethyl ether
5. washThe combined organic phases were washed once with aqueous 1M sodium hydroxide solution and once with brine
6. dry with materialThe organic phase was dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. additionUpon addition of ethanol to the resulting residue a white solid
10. customformed
11. customThe solid was collected
12. customdried under high vacuum

ORD record

ord-c09e0f190df147ab88d149c61574be4c

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08080580B2