Ethyl formate → 4-Chloropyridine-3-carbaldehyde

Participants

Reaction Conditions

Reaction Steps

4-Chloropyridine (3.1 g, 27.3 mmol, after drying over Na2SO4) was extracted from a mixture of 4-chloropyridine hydrochloride in 5% NaHCO3 with methylene chloride, dissolved in THF (50 mL), and cooled to −78° C. under dry nitrogen, followed by addition of LDA (1.5 M in cylclohexane, 18.2 mL). After 4 hours at −78° C., excess ethyl formate was added quickly. After 3 hours at −78° C., the reaction was allowed to warm to ambient temperature overnight. The reaction was diluted with water and extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, chromatographed (20% EtOAc in hexanes), and dried under high vacuum to give 1.47 g of the aldehyde. MS m/e 142 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ 7.44 (d, 1H, J=6 Hz), 8.69 (d, 1H, J=6 Hz), 9.06 (s, 1H), 10.51 (s, 1H).

Provenance & Evidence