反应详情

温度

0 °C

To triethyl orthoformate (20.2 mL, 121.5 mmol) in dry dichloromethane (115 mL) under argon at −10° C. was added drop-wise BF3.OEt2 (15.4 mL, 121.5 mmol). The solution was allowed to warm to 0° C. and was stirred for 10 minutes. After, the solution was cooled to −78° C. prior to the slow drop-wise addition of tert-butyl 6-fluoro-4-oxo-spiro[chromane-2,4′-piperidine]-1′-carboxylate (13.6 g, 40.5 mmol) in dichloromethane (10 mL). iPr2NEt (24.7 mL, 141.7 mmol) was added drop-wise over 30 minutes, and the mixture was slowly warmed to room temperature and was stirred at 25° C. for 2 hours. The reaction mixture was diluted with the addition of dichloromethane (200 mL) followed by saturated aqueous sodium bicarbonate solution (200 mL). The mixture was shaken in a separatory funnel and separated. The organic layer was washed with additional sodium bicarbonate solution (200 mL) and brine (200 mL). The organic layer was dried over sodium sulfate, filtered and concentrated to yield a residue that was purified by silica gel column chromatography (0-25% EtOAc/hexanes gradient) to give tert-butyl 3-(diethoxymethyl)-6-fluoro-4-oxospiro[chroman-2,4′-piperidine]-1′-carboxylate (3.9 g, 22%). ESI-MS m/z calc. 437.2. found 438.7 (M+1)+. Retention time 2.14 minutes (3 min run).

1. temperatureAfter, the solution was cooled to −78° C.
2. temperaturethe mixture was slowly warmed to room temperature
3. stirringwas stirred at 25° C. for 2 hours
4. stirringThe mixture was shaken in a separatory funnel
5. customseparated
6. washThe organic layer was washed with additional sodium bicarbonate solution (200 mL) and brine (200 mL)
7. dry with materialThe organic layer was dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customto yield a residue that
11. customwas purified by silica gel column chromatography (0-25% EtOAc/hexanes gradient)