反应详情

温度

25 °C

To a solution of tert-butyl 3-(diethoxymethyl)-6-fluoro-4-oxo-spiro[chromane-2,4′-piperidine]-1′-carboxylate (2.6 g, 6.0 mmol) in ethanol (20 mL) was added hydrochloric acid (22.5 mL of 4 M, 89.8 mmol) (4 M in dioxane). The reaction mixture was allowed to stir at 25° C. for 2 hours. The solvent was removed under vacuum, and the obtained solid was azeotroped with ethanol (3×30 mL). The resulting beige-white solid was fully dissolved in ethanol (21 mL) at 25° C. prior to the addition of tert-butyl N-amino-N-methyl-carbamate (1.1 mL, 7.2 mmol). The solution was allowed to stir overnight. To the thick beige-white slurry that formed was added hydrochloric acid (7.5 mL of 4 M, 29.9 mmol) (4 M in dioxane). The mixture was heated at 60° C. to yield a clear yellow solution. After 1 hour at 60° C., a white thick slurry developed. The slurry was allowed to slowly cool to 25° C. over 4 hours, and solids were collected by vacuum filtration. The cake was rinsed with a 10% solution of ethanol in hexanes (2×). Residual solvents were further removed under reduced pressure providing 8-fluoro-1-methyl-spiro[chromeno[4,3-c]pyrazole-4,4′-piperidine]hydrochloride (1.9 g, 92%). 1H NMR (400 MHz, DMSO) δ 7.59 (dd, J=9.3, 2.8 Hz, 1H), 7.43 (s, 1H), 7.27-7.10 (m, 2H), 4.12 (s, 3H), 3.28-3.11 (m, 4H), 2.59 (s, 1H), 2.22-2.02 (m, 4H). ESI-MS m/z calc. 273.1. found 274.1 (M+1)+. Retention time 0.84 minutes (3 min run).

1. customThe solvent was removed under vacuum
2. customthe obtained solid was azeotroped with ethanol (3×30 mL)
3. dissolutionThe resulting beige-white solid was fully dissolved in ethanol (21 mL) at 25° C.
4. stirringto stir overnight
5. customTo the thick beige-white slurry that formed
6. temperatureThe mixture was heated at 60° C.
7. customto yield a clear yellow solution
8. waitAfter 1 hour at 60° C.
9. temperatureto slowly cool to 25° C. over 4 hours
10. filtrationsolids were collected by vacuum filtration
11. washThe cake was rinsed with a 10% solution of ethanol in hexanes (2×)
12. customResidual solvents were further removed under reduced pressure