4-Bromoanisole → 4-(4-Methoxyphenyl)pyridine

Participants

Reaction Conditions

Reaction Steps

A solution of 4-methoxyphenylmagnesium bromide, prepared from 4-bromoanisole (150 g 0.80 mol) and magnesium (20 g, 0.83 mol) in dry tetrahydrofuran (300 mL) is filtered, cooled to −10° C. and added cautiously to a stirred mixture of bis-(triphenylphosphine)nickel (II) chloride (1.5 g 2.25 mmol) and 4-bromopyridine hydrochloride (65 g, 0.334 mol) in dry tetrahydrofuran (300 mL) at 10° C. under an argon atmosphere. After 50% of the Grignard reagent had been added a vigorous, exothermic reaction sets in and the temperature of the mixture is maintained between 50 and 60° C. throughout the rest of the addition by employing an ice-methanol cooling bath. When the addition is complete the mixture is stirred for 60 min at 50° C. The solvent is evaporated off under reduced pressure to yield a residue which is treated with t-butylmethylether (500 mL) and extracted with hydrochloric acid (3×300 mL of 5M). The combined extracts are washed (t-butylmethylether), basified (aqueous NaOH) and extracted with t-butylmethylether (4×300 mL). The combined extracts are dried (Na2SO4) and the solvent is evaporated off under reduced pressure to yield the crude product which is purified by recrystallisation from t-butylmethylether-cyclohexane to give 4-(4-methoxyphenyl)pyridine as a colourless crystalline solid, m.p. 94-96° C.

Provenance & Evidence