反应详情

1-[4-(2-Carbamoylpyridin-4-yloxy)-2-fluorophenylcarbamoyl]cyclopropanecarboxylic acid benzyl ester (10 g) was dissolved in N,N-dimethylformamide (100 ml) at room temperature, and water (2.41 ml) was added. Iodobenzene diacetate (7.91 g) was added with stirring at room temperature, the reaction mixture was stirred for 3 hours, iodobenzene diacetate (360 mg) was further added, and the reaction mixture was stirred for 2 hours. Ethyl acetate (100 ml) and a 5% aqueous solution of sodium hydrogencarbonate (100 g) were added to the reaction mixture, and layers were separated. The organic layer was washed with water, dried over magnesium sulfate, filtered, and concentrated. Ethyl acetate (30 ml) was added to the resultant crude crystals, and the mixture was heated and stirred at 60° C. After confirming the crystals were dissolved, the mixture was allowed to cool down to room temperature. Seed crystals obtained in Method 1 (50 mg) were added, and the mixture was stirred for 30 minutes. After confirming the precipitation of the crystals, heptane (100 ml) was added, and the mixture was further stirred for 30 minutes. The crystals were collected by filtration and dried to give the title compound (6.84 g).

1. stirringthe reaction mixture was stirred for 3 hours
2. stirringthe reaction mixture was stirred for 2 hours
3. customwere separated
4. washThe organic layer was washed with water
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. additionEthyl acetate (30 ml) was added to the resultant crude crystals
9. temperaturethe mixture was heated
10. stirringstirred at 60° C
11. dissolutionwere dissolved
12. temperatureto cool down to room temperature
13. additionSeed crystals obtained in Method 1 (50 mg) were added
14. stirringthe mixture was stirred for 30 minutes
15. customthe precipitation of the crystals, heptane (100 ml)
16. additionwas added
17. stirringthe mixture was further stirred for 30 minutes
18. filtrationThe crystals were collected by filtration
19. customdried