反应详情

温度

80 °C

A hydrogenation apparatus is charged with 6 g of ethyl 6-nitrochromone-2-carboxylate (Example 10), 3.5 mL of acetic anhydride, 1 g of 10% palladium on carbon, 4.0 g of dry, powdered 3A molecular sieves, and 30 mL of glacial acetic acid. After purging several times with nitrogen, the apparatus is purged several times with hydrogen. Under continuous stirring, the apparatus is maintained at about 70 psi with hydrogen and about 80° C. for about 10-12 h. The apparatus is then cooled to about 50° C., evacuated of hydrogen, and purged several times with nitrogen. Trifluororoacetic acid (3.5 mL) is added to the mixture, then the apparatus is resealed, purged several times with hydrogen, and pressurized to 70 psi with hydrogen. The stirred reaction mixture is heated to 80° C. until the reaction is complete by HPLC (intermediate:product≦3%), then cooled to room temperature. After filtering the mixture through Celite, the catalyst and molecular sieves are washed with 10 mL aliquots of glacial acetic acid, and the washes combined with the filtrate. These combined filtrates are concentrated by mild distillation to an oil, which is dissolved in ethyl acetate and washed with saturated NaHCO3. The aqueous fraction is extracted with ethyl acetate, then made strongly acidic with concentrated HCl and extracted several times with ethyl acetate. The combined ethyl acetate fractions are combined and concentrated to a solid. The solid is washed with acetonitrile, filtered, and dried to afford about 3.5-4.0 g of ethyl 6-acetamidochromane-2-carboxylate as a white solid.

1. customof dry
2. customAfter purging several times with nitrogen
3. customthe apparatus is purged several times with hydrogen
4. temperatureThe apparatus is then cooled to about 50° C.
5. customevacuated of hydrogen
6. custompurged several times with nitrogen
7. additionTrifluororoacetic acid (3.5 mL) is added to the mixture
8. custompurged several times with hydrogen
9. customThe stirred reaction mixture
10. temperatureis heated to 80° C. until the reaction
11. temperaturecooled to room temperature
12. filtrationAfter filtering the mixture through Celite
13. washthe catalyst and molecular sieves are washed with 10 mL aliquots of glacial acetic acid
14. concentrationThese combined filtrates are concentrated by mild distillation to an oil, which
15. dissolutionis dissolved in ethyl acetate
16. washwashed with saturated NaHCO3
17. extractionThe aqueous fraction is extracted with ethyl acetate
18. extractionextracted several times with ethyl acetate
19. concentrationconcentrated to a solid
20. washThe solid is washed with acetonitrile
21. filtrationfiltered
22. customdried