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

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Reaction Conditions

Reaction Steps

To a flask equipped with a reflux condenser, mechanical stirring, and internal temperature probe was added potassium 2-chloro-3-ethoxy-3-oxoprop-1-en-1-olate (58.70 g, 311.1 mmol) followed by 200 mL of EtOH. Aqueous hydrogen chloride (4.862 ml, 15.56 mmol) in EtOH was 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. An additional 30 g of potassium 2-chloro-3-ethoxy-3-oxoprop-1-en-1-olate were added and the mixture was stirred at 70° C. for 2 hours. The mixture was cooled to ambient temperature and 500 mL of water added, followed by pH adjustment 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 title compound.

Provenance & Evidence