Methyl iodide → 4-Bromo-2-fluoro-3-methylbenzonitrile

Temperature

0 °C

To a solution of DIPA (12.1 g, 0.120 mmol) in 20 mL of dry THF was added 2.5M of n-BuLi (44 mL, 0.11 mmol) dropwise under Ar at −78° C., and then the reaction was allowed to warm to 0° C. After stirring for 1 hour, the solution was added to a solution of 4-bromo-2-fluorobenzonitrile (20 g, 0.1 mmol) in 200 mL of dry THF dropwise at −78° C. under Ar and the mixture was stirred for 3 hours, then MeI (15.6 g, 0.110 mmol) was added at one portion and the mixture was stirred for another 30 minutes. Then the reaction was quenched with aq. NH4Cl and extracted with EtOAc (200 mL×3). The combined organic layers were washed with water, brine, dried and concentrated to brown oil, which was purified by silica gel column to give 4-bromo-2-fluoro-3-methylbenzonitrile.

1. stirringthe mixture was stirred for 3 hours
2. stirringthe mixture was stirred for another 30 minutes
3. customThen the reaction was quenched with aq. NH4Cl
4. extractionextracted with EtOAc (200 mL×3)
5. washThe combined organic layers were washed with water, brine
6. customdried
7. concentrationconcentrated to brown oil, which
8. customwas purified by silica gel column

ORD record

ord-f59217b8c99c45378d88b1046a634caa

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09018211B2