Dimethylformamide → tert-Butyl 4-chloro-3-formylpyridin-2-ylcarbamate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of tert-butyl (4-chloropyridin-2-yl)carbamate (1.00 g, 4.37 mmol) in THF (30 mL) cooled to −78° C. was added n-butyllithium (2.55 M in hexane, 4.1 mL, 10.06 mmol) dropwise. After complete addition the solution was stirred at −78° C. for 1 h. DMF (1.591 mL, 20.55 mmol) was added dropwise and the resultant solution stirred at −78° C. for an additional 1 h. The reaction mixture was then quenched by addition of saturated aqueous ammonium chloride solution (20 mL) and extracted with ethyl acetate (2×25 mL). The combined organic extracts were washed with brine (1×20 mL), dried over sodium sulfate and concentrated under reduced pressure. The crude residue was purified via neutral alumina chromatography (ethyl acetate/hexanes) to yield tert-butyl (4-chloro-3-formylpyridin-2-yl)carbamate (530 mg, 2.06 mmol, 27% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 10.73 (s, 1H), 10.55 (s, 1H), 8.52 (d, J=5.3 Hz, 1H), 7.06 (d, J=5.3 Hz, 1H), 1.56 (s, 9H); LC/MS (ESI) m/e 255.2 [(M−H)−, calcd for C11H12ClN2O3 255.1]. LC/MS retention time (method A): tR=1.75 min.

Provenance & Evidence