Chloroacetaldehyde → 5-Chloroimidazo[1,2-a]pyridine hydrochloride

Participants

Reaction Steps

To a stirred solution of 2-amino-6-chloropyridine (20.00 g, 156 mmol) in ethanol (300 mL) at ambient temperature was added chloroacetaldehyde (26.1 mL of a 50% aqueous solution, 202 mmol). The reaction mixture was heated at refux for 5 h, allowed to cool to ambient temperature and concentrated in vacuo. The residue was treated with dichloromethane (400 mL) and the dichloromethane layer was decanted. The resultant brown gummy solid was treated with a mixture of methanol (20 mL) and diethyl ether (500 mL). The colorless solid so obtained was collected by filtration to afford 5-chloroimidazo[1,2-a]pyridine hydrochloride (13.26 g, 45% yield). The filtrate was combined with the aforementioned dichloromethane layer and the mixture concentrated in vacuo. The residue was dissolved in dichloromethane (500 mL). The resulting solution was washed with saturated aqueous sodium bicarbonate and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with a 40-95% gradient of ethyl acetate in hexanes to afford a second batch of 5-chloroimidazo[1,2-a]pyridine as a brown liquid in 39% yield (9.18 g): 1H NMR (300 MHz, DMSO-d6) δ8.02 (s, 1H), 7.74 (s, 1H), 7.65 (d, J=9.0 Hz, 1H), 7.31 (dd, J=7.5, 7.5 Hz, 1H), 7.19 (d, J=7.2 Hz, 1H); MS (ES+) m/z 153.0 (M+1), 155.0 (M+1).

Provenance & Evidence