反应详情

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).

1. temperatureheated to 35° C. for 20 hours
2. temperatureThe mixture was cooled to ambient temperature
3. customto precipitate the product
4. filtrationThe solids were collected by filtration
5. washwashed with water (4000 mL)
6. dry with materialThe material was dried under vacuum at 40° C. to the crude product (174.1 g, 100% yield)
7. customThe crude material was further purified
8. dissolutionby dissolving the material in IPA (220 mL) at 65° C
9. additionAt 65° C., water (130 mL) was added to the solution (
10. temperaturemaintaining a temperature>60° C.)
11. temperatureThe solution was slowly cooled over four hours to 20° C., during which time solid product
12. customcrystallized out of the solution
13. temperatureThe mixture was cooled to 10° C.
14. stirringstirred for 16 hours
15. filtrationThe solids were collected by filtration
16. washwashed with 10% IPA/water (v:v) (1000 mL)
17. customThe material was dried under vacuum at 40° C.