Dimethylformamide → 6-Bromo-3-pyridinecarboxaldehyde

Participants

Reaction Conditions

Reaction Steps

40.1 ml of a 2M solution of n-butylmagnesium chloride in THF (80.2 mmol) were added to a solution 100.2 ml of a 1.6M solution of n-butyllithium in hexane (160.41 mmol) in 50 ml of toluene and 50 ml of THF at −10° C. to 0° C. over 0.5 h, and the mixture was stirred at −10° C. for 0.5 h. A solution of 50 g (211 mmol) of 2,5-dibromopyridine in 200 ml of toluene and 200 ml of THF was added dropwise over 1 h while maintaining the temperature of the mixture below −5° C. The resulting suspension was stirred at −10° C. for 2.5 h and then transferred into a cooled (−10° C.) solution of 21.2 ml of DMF (274.3 mmol) in 100 ml of toluene and 100 ml of THF over 0.5 h. The mixture was left at −10° C. to −5° C. for 0.5 h and then quenched with 400 ml of water. After stirring the mixture below 20° C. for 10 min, the organic layer was separated and the aqueous layer was extracted three times with 400 ml each of ethyl acetate. The combined extracts were dried over sodium sulfate and concentrated in vacuo. The residue was purified by chromatography (silica gel, cyclohexane/ethyl acetate 9:1) to give 23.9 g (60.8%) of the title compound as a white solid.

Provenance & Evidence