Cesium fluoride → 3-(4-Hydroxyphenyl)benzonitrile

Participants

Reaction Steps

A 250 mL flask was charged with 2.21 g (2.7 mmol) (1,1′-bis(diphenylphosphino) ferrocene) dichloropalladium (II)•dichloromethane, 6.26 g (2.73 mmol) 3-iodobenzonitrile, 6.0 g (3.95 mmol) 4-methoxyphenylboronic acid, and 12.45 g (8.20 mmol) cesium fluoride, followed by the addition of 180 mL 1,2-dimethoxyethane. The flask was flushed with N2 and the suspension heated to reflux which was maintained for 3 hours. The reaction mixture was cooled to room temperature, filtered through a pad of 300 g flash silica gel, and the pad was washed with 1 L ethyl acetate. The ethyl acetate was concentrated and the residue purified by flash chromatography on silica gel eluting with 10% hexanes/90% ethyl acetate to give 3.3 g of the desired product (58% yield). This material was dissolved in 50 mL anhydrous dichloromethane and the solution cooled in a dry ice-acetone bath and a solution of boron tribromide (40 mL, 4 mmol) was added dropwise under inert atmosphere. The reaction was then stirred at room temperature overnight. The solution was cooled in an ice bath and 5 mL of H2O was added dropwise, followed by the addition of 20 mL 1N HCl. The mixture was stirred for 1 hour and the resulting suspension was filtered and the filtrate transferred to a separatory funnel and the organic layer separated off and set aside. The filtered solid was washed with H2O and ethyl acetate and filtered and the filtrate transferred to the separatory funnel and the organic layer combined with the previous organic layer, dried over Na2SO4, filtered and the filtrate concentrated to provide 3.05 g of the desired product (99% yield).

Provenance & Evidence