Dimethylformamide → 6-Bromo-3-pyridinecarboxaldehyde

Participants

Reaction Conditions

Reaction Steps

n-Butylmagnesium chloride (4.00 mmol) in 2.00M tetrahydrofuran solution (2.00 mL) was added to ice-cooled n-butyllithium (8.06 mmol) in 1.55M hexane (20 mL). The mixture was stirred at 0° C. for 15 minutes to give a suspension. The suspension was added to a mixture of toluene (15 mL) and tetrahydrofuran (10 mL) containing 2,5-dibromopyridine (2.37 g, 10.0 mmol) over a period of 10 minutes or more while keeping the temperature below −5° C. to give a dark orange solution. The solution was stirred at 0° C. for 1.25 hours and then at 20° C. for one hour. The solution was cooled to 0° C., and N,N-dimethylformamide (1.0 mL, 13 mmol) was added thereto. After the mixture was stirred at 0° C. for 30 minutes, 1M aqueous acetic acid solution (20 mL) was added. The organic phase was separated, and the aqueous phase was extracted twice with ethyl acetate (10 mL). The organic phases were combined, washed with saturated aqueous sodium chloride (15 mL), dried over magnesium sulfate and concentrated under reduced pressure to remove the solvent. The resultant residue was purified by flash column chromatography on silica gel in a developing solvent system of hexane-ethyl acetate (20:1, v/v) to give the title compound (1.229 g, 66% yield) as a colorless solid.

Provenance & Evidence