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

関与物質

反応手順

Potassium (E)-2-chloro-3-ethoxy-3-oxoprop-1-en-1-olate (300.8 g, 1594 mmol) was suspended in acetonitrile (800 mL) and 12.1 M aqueous HCl (32.1 mL, 388.9 mmol) was added slowly. The mixture was stirred at ambient temperature for 15 minutes. 4-Chloropyridin-2-amine (100 g, 777.8 mmol) was added to the mixture and heated to 35° C. for 20 hours. The mixture was cooled to ambient temperature and water (2500 mL) was added. The pH of the mixture was adjusted to 8.0-8.5 with 2.5 N aqueous NaOH (100 mL, 250 mmol) to precipitate the product. The solids were collected by filtration and washed with water (4000 mL). The material was dried under vacuum at 40° C. to the crude product (174.1 g, 100% yield). The crude material was further purified by dissolving the material in IPA (220 mL) at 65° C. At 65° C., water (130 mL) was added to the solution (maintaining a temperature>60° C.). The solution was slowly cooled over four hours to 20° C., during which time solid product crystallized out of the solution. The mixture was cooled to 10° C. and stirred for 16 hours. The solids were collected by filtration and washed with 10% IPA/water (v:v) (1000 mL). The material was dried under vacuum at 40° C. to give the purified product (134 g, 76.6% yield).

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