Bromine → 2-Bromo-3,4-difluoro-1-methoxy-benzene

To a solution of 3,4-difluoroanisole (2 mL) in tetrahydrofuran (50 mL) was added n-butyllithium (2.67 mol/L n-hexane solution, 6.95 mL) at −78° C., and the mixture was stirred at the same temperature for 30 minutes. To the reaction mixture was added bromine (1.04 mL), and the mixture was stirred at −78° C. for 15 minutes. The mixture was stirred under ice-cooling for 1 hour. To the reaction mixture was added a saturated aqueous ammonium chloride solution, and the resulting mixture was extracted with diethyl ether. The extract was washed with a saturated aqueous sodium hydrogen carbonate solution and brine successively, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane −n-hexane/ethyl acetate=9/1) to give the title compound (0.91 g)

1. stirringthe mixture was stirred at −78° C. for 15 minutes
2. stirringThe mixture was stirred under ice-
3. temperaturecooling for 1 hour
4. extractionthe resulting mixture was extracted with diethyl ether
5. washThe extract was washed with a saturated aqueous sodium hydrogen carbonate solution and brine successively
6. dry with materialdried over anhydrous sodium sulfate
7. customThe solvent was removed under reduced pressure
8. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane −n-hexane/ethyl acetate=9/1)

ORD record

ord-464f252c43b343b488a8bf0835df7f60

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09040693B2