Tris(1,1-dimethylethyl)phosphine → 4,2',6'-Trifluorobiphenyl-2-carbonitrile

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Reaction Steps

A suspension of 2-bromo-5-fluorobenzonitrile (10.0 g, 50 mmol), potassium fluoride (9.59 g, 165 mmol) and 2,6-difluorophenylboronic acid (9.87 g, 62.5 mmol) in tetrahydrofuran (120 ml) and water (15 ml) was degassed with nitrogen for 30 min. Tris(dibenzylidineacetone)dipalladium(0) (916 mg, 1.0 mmol) and tri-tert-butylphosphine (10% w/w solution in hexane, 0.5 ml) were added and the mixture stirred at ambient temperature for 18 h. The black solution was washed with 1N sodium hydroxide solution (2×100 ml), and the aqueous phase was re-extracted with diethyl ether (100 ml). The organic layers were combined, washed with brine (50 ml), filtered through a glass microfibre filter paper then evaporated to give an orange solid. The solid was suspended in 2-propanol (120 ml) and heated to 70° C. to aid dissolution. The solution was left to cool to ambient temperature then water (120 ml) was added dropwise over 1 h. The resulting solid was collected by filtration, washed with 2-propanol/water (1:1, 30 ml) then dried under vacuum to give 4,2′,6′-trifluorobiphenyl-2-carbonitrile (9.92 g, 85 %) as a grey solid: δH (360 MHz, CDCl3) 7.06 (2H, t, J 7.9), 7.38–7.52 (4H, m).

Provenance & Evidence