Hydrochloric Acid → Ethyl 7-chloroimidazo[1,2-A]pyridine-3-carboxylate

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Reaction Conditions

Reaction Steps

A flask equipped with a reflux condenser, mechanical stirring, and an internal temperature probe, was charged with potassium 2-chloro-3-ethoxy-3-oxoprop-1-en-1-olate (58.70 g, 311.1 mmol) followed by addition 200 mL of EtOH to form a slurry. Aqueous hydrogen chloride (4.862 mL, 15.56 mmol) in EtOH was then added to the slurry. The slurry was stirred for about 15 minutes, and then 4-chloropyridin-2-amine (20.00 g, 155.6 mmol) was added, and the mixture was warmed to 70° C. After about one hour, an additional 2 equivalents of 3.2 M aqueous HCl were added and the mixture stirred at 70° C. for 16 hours. At this point, an additional 30 g of potassium 2-chloro-3-ethoxy-3-oxoprop-1-en-1-olate were added and the mixture stirred at 70° C. for 2 hours to facilitate completion of the reaction. The mixture was cooled to ambient temperature and 500 mL of water were added, followed by adjustment of the pH to 11 with 10% aqueous sodium carbonate. After stirring for several hours, the precipitated solids were collected by filtration and dried under vacuum to give 31 g (88%) of the desired compound.

Provenance & Evidence