反应详情

To a solution of (3 aR,4R,5R,6S,7aS)-6-(difluoromethyl)-2-(methylthio)-3a,4,5,6,7,7a-hexahydrobenzo[d]oxazole-4,5-diol (52.6 mg, 0.208 mmol) in EtOH (5 mL) was added azetidine hydrochloride (97 mg, 1.04 mmol). The mixture was heated at reflux for 5 h. After cooling, solid NaHCO3 (200 mg, 2.38 mmol) was added and stirred for 10 min Solvent was evaporated and the residue was purified by silica gel column chromatography, eluted with 5% 2 M NH3 MeOH solution in DCM to give the product (3aR,4R,5R,6S,7aS)-2-(azetidin-1-yl)-6-(difluoromethyl)-3a,4,5,6,7,7a-hexahydrobenzo[d]oxazole-4,5-diol (46.2 mg, 85%) as a white solid. MS m/z 263.1 (M+1, 100%); 1H NMR (400 MHz, MeOD) δ 6.14 (td, J=56.8 Hz, 1.8 Hz, 1H), 4.66-4.69 (m, 1H), 4.00 (t, J=7.6 Hz, 4H), 3.62 (t, J=7.2 Hz, 1H), 3.34 (t, J=9.2 Hz, 1H), 3.24 (t, J=7.9 Hz, 1H), 2.29-2.36 (m, 2H), 2.21 (dt, J=15.1 Hz, 3.6 Hz, 1H), 1.95-2.10 (m, 1H), 1.82-1.90 (m, 1H); 13C NMR (100 MHz, MeOD) δ 164.62, 117.96 (t, J=238.5 Hz), 81.20, 79.89 (d, J=1.6 Hz), 71.36 (dd, J=7.2 Hz, 1.0 Hz), 68.72, 51.91, 42.25 (t, J=19.8 Hz), 22.61 (t, J=4.7 Hz), 17.75.

1. temperatureThe mixture was heated
2. temperatureat reflux for 5 h
3. temperatureAfter cooling
4. customwas evaporated
5. customthe residue was purified by silica gel column chromatography
6. washeluted with 5% 2 M NH3 MeOH solution in DCM