Carbon Dioxide → 4-Chloronicotinic acid

Participants

Reaction Steps

4-Chloropyridine hydrochloride (25 g) is neutralized with aq. Na2CO3 (10%) and extracted with DCM. The organic layer is separated, dried over Na2SO4 and concentrated under reduced pressure to afford 4-chloropyridine (19 g). To a solution of diisopropylamine (31 mL, 217.6 mmol) in dry THF is added n-butyllithium (115 mL, 184.1 mmol) dropwise at −78° C. under nitrogen. After 30 min, a solution of 4-chloropyridine (19 g, 167.4 mmol) in dry THF is slowly added under nitrogen. The reaction mixture is further stirred for 1 h at −78° C. before addition of solid CO2, let warmed to RT and stirred at RT for 12 h under nitrogen. After this time, reaction mixture is concentrated under reduced pressure and acidified with aq. HC1 solution (1.5 N) under ice-cooled condition. Precipitate is filtered under reduced pressure and dried overnight under vacuum to afford 15 g (57%) of the title compound. 1H NMR (DMSO-d6, 400 MHz): δ 6 13.83 (bs, 1H), 8.92 (s, 1H), 8.64-8.63 (d, J=5.4 Hz, 1H), 7.66-7.65 (d, J=5.4 Hz, 1H).

Provenance & Evidence