Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[F:10].[Li]CCCC.[F:16][CH:17]([F:23])[C:18](OCC)=[O:19]>CCOCC>[F:16][CH:17]([F:23])[C:18]([C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[F:10])=[O:19]To 1-bromo-2-fluoro-4-methoxybenzene (123 g, 0.6 mol) in 1300 mL Et2O at −78° C. was added n-BuLi (276 mL, 2.5 M) dropwise. After stirring at −78° C. for 2 hours, ethyl difluoroacetate (82.6 g, 0.67 mol) was added dropwise at −78° C. The reaction was stirred overnight at 25° C., and was quenched with saturated ammonium chloride solution at −20° C., followed by 1N HCl (final pH=4). The organic layer was separated and aqueous layer was extracted with Et2O. The combined extracts were dried over MgSO4, filtered and concentrated, and the residue was purified by column chromatography (PE/EA 20:1) to afford 2,2-difluoro-1-(2-fluoro-4-methoxyphenyl)ethanone as an oil.
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