Ethyl difluoroacetate → 2,2-Difluoro-1-(2-fluoro-4-methoxyphenyl)ethan-1-one

HRID 216337Notes

Reaction equation

HRID 216337 reaction equation
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]

Participants

5

Reactant 3

HCID 9961Ethyl difluoroacetateHCID 37184441-Bromo-2-fluoro-4-methoxybenzeneHCID 178418339Butyllithium

Product 1

HCID 866384912,2-Difluoro-1-(2-fluoro-4-methoxyphenyl)ethan-1-one

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

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.

Workup

  1. stirringThe reaction was stirred overnight at 25° C.
  2. customwas quenched with saturated ammonium chloride solution at −20° C.
  3. customThe organic layer was separated
  4. extractionaqueous layer was extracted with Et2O
  5. dry with materialThe combined extracts were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customthe residue was purified by column chromatography (PE/EA 20:1)

Sources & evidence

ORD record
ord-7e606834702e46d0bb50c2892372d5be
Source dataset
uspto-grants-2012_06
Patent number
US08193228B2

Reaction notes

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