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 1N 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 1N 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