Sodium Hydroxide → Methyl 5-chloroimidazo[1,5-a]pyridine-6-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a suspension of 2-chloro-6-formylaminomethylnicotinic acid methyl ester (42.6 g, 0.19 mol) in toluene (400 mL) was added phosphorous (V) oxychloride (18.2 mL, 0.20 mol) and the reaction mixture heated at 65° C. for 1.5 hours. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (200 mL) before treating with sodium hydroxide solution (2 M) to adjust pH˜8. The layers were separated and the aqueous layer extracted with ethyl acetate (2×100 mL). The combined organic extracts were washed with brine (100 mL), dried (MgSO4) then charcoal (˜5 g) was added and the solution mixed for 5 minutes before being filtered and concentrated in vacuo to yield the title compound as a tan solid (34.4 g, 88%) 1H NMR (CDCl3, 400 MHz) 8.52 (1H, s), 7.57 (1H, s), 7.45 (1H, d, J=9.3 Hz), 7.25 (1H, d, J=9.1 Hz), 3.97 (3H, s).

Provenance & Evidence