Water → 1-(2',4'-Difluoro-1,1'-biphenyl-2-yl)ethanone

Participants

Reaction Conditions

Reaction Steps

2,4-Difluorophenylboronic acid (9.47 g, 60 mmol), tetrabutylammonium bromide (16.1 g, 50 mmol), and potassium carbonate (20.7 g, 150 mmol) were added to a flask followed by water (50 mL). The contents were mixed until most of the dissolvable solids were in solution. To the remaining slurry was added 2′-bromoacetophenone (9.95 g, 50 mmol) and palladium acetate (1.12 g, 5 mmol). The stirred contents were heated to 70° C. under a nitrogen atmosphere for 12 hours. Thin layer chromatography analysis indicated the formation of a single product. The reaction was allowed to cool to room temperature. Ethyl acetate (500 mL) was added and the organic phase was extracted with water (3×100 mL). The combined aqueous phase was extracted once with additional ethyl acetate and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated to provide a crude oil. The product was purified by preparative liquid chromatography on a Biotage® 40 Mi column of prepacked silica gel (90 g), eluting with a gradient of 5%-20% methyl tert-butyl ether in hexane, to afford the title compound (5.7 g, 49%) as a yellow oil;

Provenance & Evidence