2-Bromobenzonitrile → 2-(2-Fluorophenyl)benzonitrile

Participants

Reaction Steps

A mixture of 2-bromobenzonitrile (5.1 g, 28 mmol), 2-fluorobenzeneboronic acid (4.9 g, 35 mmol) and potassium fluoride (5.37 g, 92 mmol) in tetrahydrofuran (50 ml) was degassed with nitrogen for 10 min. This mixture was then treated with tris(dibenzylideneacetone)dipalladium(0) (510 mg, 0.56 mmol) followed by tri-tert-butylphosphine (5.6 ml of a 0.2M solution in 1,4-dioxane, 1.12 mmol) and the reaction was stirred at ambient temperature for 15 min. The resulting slurry was then heated at 50° C. for 30 min in order to consume remaining starting materials and then cooled to ambient temperature. The reaction mixture was filtered, washing the filter-cake with tetrahydrofuran (50 ml). The filtrate was evaporated to dryness and the residue partitioned between ethyl acetate and water. The organics were washed with brine, dried over anhydrous magnesium sulfate, filtered and pre-adsorbed onto silica. Purification by chromatography on silica eluting with isohexane on a gradient of ethyl acetate (5-10%) gave 2′-fluorobiphenyl-2-carbonitrile as a pale yellow solid (5.5 g, 100%): δH (360 MHz, CDCl3) 7.19-7.29 (2H, m), 7.40-7.52 (4H, m), 7.65 (1H, ddd, J 8, 8 and 1), 7.79 (1H, dd, J 8 and 1).

Provenance & Evidence