Dimethylformamide → 3-Chloropyrazine-2-carbaldehyde

Participants

Reaction Conditions

Reaction Steps

A flame dried and cooled 100 mL round bottom flask was charged with 2,2,6,6-tetramethylpiperidine (2.5 mL, 14.96 mmol) and anhydrous THF (25 mL) under a nitrogen atmosphere. The contents were cooled to −78° C. and n-butyllithium (2.5 M in hexane, 5.7 mL, ˜14.28 mmol) was added dropwise over a 5 minute period. The reaction mixture was stirred at −78° C. for 5 minutes, bought to 0° C. and stirred at 0° C. for 25 minutes. The reaction mixture was recooled to −78° C. and 2-chloropyrazine (0.78 g, 1 mL, 6.8 mmol) was added over a 3 minute period. After 30 minutes at −78° C., anhydrous DMF (0.99 mL, 13.6 mmol) was added over 3 minutes and the contents stirred at −78° C. for a further 30 minutes. The reaction mixture was bought to 0° C., stirred at 0° C. for 15 minutes, recooled to −78° C. and quenched by the addition of acetic acid (4 mL) in THF (10 mL). The reaction mixture was stirred at room temperature for 10 minutes and partitioned between ethyl acetate (60 mL) and brine (30 mL). The ethyl acetate layer is separated, dried over sodium sulfate, concentrated under reduced pressure and purified by silica gel flash chromatography using dichloromethane and ethyl acetate (9.5:0.5, 400 mL) to yield the title compound a (950 mg). 1H-NMR of the compound was consistent with the desired structure.

Provenance & Evidence