反应详情

温度

80 °C

To a solution of tert-butyl 4-oxopiperidine-1-carboxylate (12.1 g, 60.9 mmol) in pyrrolidine (7.3 mL, 87.2 mmol) and anhydrous methanol (16.5 mL) was added 1-(5-fluoro-2-hydroxy-phenyl)ethanone (9.3 g, 60.7 mmol). The reaction mixture was stirred at 80° C. for 2.5 hours. The methanol was removed under reduced pressure and the resulting residue was dissolved in ethyl acetate (150 mL), washed with 1 N HCl (1×150 mL) and brine (2×100 mL). The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to yield a yellow oil. The oil was diluted with hexanes (400 mL) and was heated at 60° C. until in solution. Once dissolved, the solution was allowed to cool to 25° C. The crystals were collected via vacuum filtration, rinsed with hexanes to obtain tert-butyl 6-fluoro-4-oxo-spiro[chromane-2,4′-piperidine]-1′-carboxylate (13.6 g, 67%) as a light yellow solid. ESI-MS m/z calc. 335.2, found 336.7 (M+1)+. Retention time 1.85 minutes (3 min run).

1. customThe methanol was removed under reduced pressure
2. dissolutionthe resulting residue was dissolved in ethyl acetate (150 mL)
3. washwashed with 1 N HCl (1×150 mL) and brine (2×100 mL)
4. dry with materialThe organic layer was dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customto yield a yellow oil
8. temperaturewas heated at 60° C. until in solution
9. dissolutionOnce dissolved
10. temperatureto cool to 25° C
11. filtrationThe crystals were collected via vacuum filtration
12. washrinsed with hexanes