3-(4-Fluorobenzoyl)propyl chloride → 4-Chloro-2-fluoro-1-(4-fluorophenyl)butan-1-one

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Reaction Steps

A 1,4-dioxane (50 mL) solution of bromine (8.76 g, 54.8 mmol) was added to a 1,4-dioxane (50 mL) solution of 4-chloro-4′-fluorobutyrophenone (10.0 g, 49.8 mmol) at room temperature over 15 minutes, and the mixture was stirred at the same temperature for 10 minutes. Water was added to the reaction mixture, and the mixture was subjected to extraction twice with hexane. The organic layer thus obtained was washed with water, a saturated aqueous solution of sodium hydrogen carbonate, an aqueous solution of 1.5 M sodium sulfite, and brine, and then was dried over anhydrous sodium sulfate. A portion (13.0 g) of a crude product (14.3 g) obtained by distilling off the solvent under reduced pressure was dissolved in N,N-dimethylformamide (90 mL), and 18-crown-6 (18.4 g, 69.8 mmol) and potassium fluoride (4.05 g, 69.8 mmol) were added to the mixture at room temperature. The mixture was stirred at the same temperature for 2 and a half hours, and then 18-crown-6 (6.15 g, 23.3 mmol) and potassium fluoride (1.35 g, 23.3 mmol) were added to the mixture, and the mixture was further stirred at the same temperature for one hour. Water was added to the reaction mixture, and the mixture was subjected to extraction twice with hexane. The organic layer thus obtained was washed with water and brine, and then was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:0→95:5, v/v) to give the title compound (5.47 g, yield: 55%).

Provenance & Evidence