Citric Acid → 5-(Benzyloxy)pyridine-2-carbaldehyde

Participants

Reaction Conditions

Reaction Steps

A solution of 6-bromopyridin-3-ol (4.20 g) in N,N-dimethylformamide (100 mL) was purged with nitrogen, sodium hydride (60%, oil, 1.06 g) was added under ice-cooling, and the mixture was stirred at 0° C. for 15 min. Benzyl bromide (3.15 mL) was added to the reaction mixture, and the mixture was warmed to room temperature, and stirred at room temperature for 16 hr. A saturated aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=10:90-50:50, volume ratio) to give a colorless oil. A solution of the obtained oil in toluene (10 mL) was added to a solution of tributylmagnesium ate complex in toluene-tetrahydrofuran-hexane prepared from a 1.6M n-butyllithium hexane solution (8.4 mL) and a 2.0M butylmagnesium chloride tetrahydrofuran solution (3.4 mL) in at −10° C., and the mixture was stirred at −10° C. for 2.5 hr. N,N-dimethylformamide (1.59 mL) was added to the reaction mixture, and the mixture was warmed to room temperature and stirred at room temperature for 2 hr. 10% Aqueous citric acid solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=5:95-50:50, volume ratio) to give the title compound (1.00 g, yield 17%) as a colorless oil. MS: 214 (MH+).

Provenance & Evidence