反应详情

Morpholin-3-one (35 g, 346.2 mmol) was slurried in dry THF (350 ml). Tert-butoxycarbonyl tert-butyl carbonate (105.8 g, 111.4 mmol) was added, followed by DMAP (4.2 g, 34.6 mmol). The mixture began to degass rapidly over 30 minutes. The resulting orange solution was stirred at ambient temperature for 24 hrs. The mixture was then cooled in an ice bath and imidazole (23.57 g, 346.2 mmol) was added. After stirring for 30 minutes ethyl acetate (500 ml) was added. The organic phase was separated and washed with 1% (v/v) HCl (500 ml), then sat NaHCO3 (500 ml), then brine (200 ml), dried (MgSO4), filtered and concentrated. The crude was purified through a plug of silica gel, eluting with ethyl acetate. The filtrate was evaporated to give an oil. 40/60 pet ether (200 ml) was added slowly with stirring to generate a white solid. The mixture was aged for 30 minutes, cooled briefly in an ice bath and filtered, washing with 40/60 pet ether. Tert-butyl 3-oxomorpholine-4-carboxylate was obtained as a white solid which was dried under vacuum (52.7 g, 76%); 1H-NMR (CDCl3) 1.47 (9H, s), 3.68 (2H, m), 3.82 (2H, m), 4.15 (2H, s); MS ES(+) 145.8 (M+-tBu).

1. customto degass rapidly over 30 minutes
2. temperatureThe mixture was then cooled in an ice bath
3. additionwas added
4. customThe organic phase was separated
5. washwashed with 1% (v/v) HCl (500 ml)
6. dry with materialbrine (200 ml), dried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customThe crude was purified through a plug of silica gel
10. washeluting with ethyl acetate
11. customThe filtrate was evaporated
12. customto give an oil
13. stirringwith stirring
14. waitThe mixture was aged for 30 minutes
15. temperaturecooled briefly in an ice bath
16. filtrationfiltered
17. washwashing with 40/60 pet ether