Ethyl fluoroacetate → 1-(5-Bromo-2-fluorophenyl)-2-fluoroethanone

Participants

Reaction Conditions

Reaction Steps

A 2.0 M solution of LDA in heptane/THF/ethylbenzene (100 mL, 200 mmol) was added dropwise via syringe to a solution of 1-bromo-4-fluorobenzene (20 mL, 182 mmol) in THF (600 mL) at −78° C. After stirring for 2.5 hours at −78° C., ethyl monofluoroacetate (18.47 mL, 191 mmol) was added dropwise via syringe, and the reaction was stirred at −78° C. for 20 minutes and then stirred at −45° C. for 30 minutes before being quenched with saturated aqueous ammonium chloride at −45° C. The mixture was diluted with water and ethyl acetate. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with saturated aqueous ammonium chloride, water, and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude product was dissolved in a minimal amount of methanol and placed in a −20° C. freezer overnight. The resulting solid was collected and washed with cold methanol to afford the title intermediate (12.07 g, 51.6 mmol, 28% yield) as a white solid.

Provenance & Evidence