反应详情

Sodium hydride (1.47 g, 36.8 mmol of a 60% dispersion in oil) was added to a round-bottomed flask fitted with an N2 inlet, condensor, stirrer and washed with hexane to remove the oil. Anhydrous tetrahydrofuran (THF), 50 mL, was added followed by 6.30 grams (18.9 mmol) of (2S, 3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine in 50 mL of tetrahydrofuran. After heating to reflux for two hours, the mixture was allowed to cool to room temperature and was treated dropwise with benzyl chloromethyl ether (5.1 mL, 36.8 mmol). The mixture was stirred overnight and the excess sodium hydride quenched with water. After being stirred an additional hour, the organic layer was separated and the aqueous layer was extracted with methylene chloride. The organic layers were combined and washed with saturated aqueous sodium chloride before drying over magnesium sulfate. Concentration in vacuo gave a solid which recrystallized from methanol/methylene chloride to a white solid, 2.36 grams (40%), mp 105°-107° C. Mass Spectrum (m/e): 309 (M+1, 100%), 159 (12%). 1H-NMR (CDCl3) δ1.45-2.20 (m, 5H), 3.15 (m, 2H), 3.5 (d, 1H), 3.65-3.85 (m, 2H), 3.75 (s, 3H), 3.95 (d, 1H), 4.10 (d, 1H), 6.8 (d, 1H), 6.95 (t, 1H), 7.15-7.6 (m, 7H). Anal. Calc'd for C20 H24N2O: C, 77.88; H, 7.83, N, 9.08. Found: C, 77.72; H, 7.75; N, 9.04.

1. customfitted with an N2 inlet
2. washcondensor, stirrer and washed with hexane
3. customto remove the oil
4. additionAnhydrous tetrahydrofuran (THF), 50 mL, was added
5. temperatureAfter heating
6. temperatureto reflux for two hours
7. customthe excess sodium hydride quenched with water
8. stirringAfter being stirred an additional hour
9. customthe organic layer was separated
10. extractionthe aqueous layer was extracted with methylene chloride
11. washwashed with saturated aqueous sodium chloride
12. dry with materialbefore drying over magnesium sulfate
13. concentrationConcentration in vacuo
14. customgave a solid which
15. customrecrystallized from methanol/methylene chloride to a white solid, 2.36 grams (40%), mp 105°-107° C