反应详情

温度

100 °C

To a flask containing (5R)-1-azabicyclo[3.2.1]octan-3-one hydrochloride (3.64 g, 22.6 mmol), hydroxylamine hydrochloride (2.04 g, 29.4 mmol), and ethanol (130 mL) is added sodium acetate trihydrate (9.23 g, 67.8 mmol). The mixture stirred for 3 h and is filtered and concentrated. The resulting white solid is taken up in n-propanol (100 mL) and sodium (˜13.6 g, 618 mmol) is added in 20-25 portions. The reaction spontaneously begins to reflux, and the reaction is heated in an oil bath (100° C.). The addition is complete in ˜20 min and the mixture solidifies after ˜40 min. The oil bath is removed and n-propanol (2×25 mL) is added dissolving the remaining sodium metal. The mixture is carefully quenched through the dropwise addition of H2O (100 mL). Saturated aq. NaCl (20 mL) is added, and the layers are separated. The organic layer is dried (MgSO4), filtered, treated with freshly prepared MeOH/HCl, and concentrated. The resulting solid is triturated with 30 mL EtOH, filtered and dried in vaccuo to afford 3.51 g as a white solid: [α]25D=−3 (c 0.94, DMSO); 1H NMR (400 MHz, DMSO-d6) δ 3.60-3.80, 2.95-3.10, 2.65-2.75, 1.90-2.15, 1.70-1.90; HRMS (FAB) calcd for C7H14N2 (M+H+) 127.1235, found 127.1235.

1. filtrationis filtered
2. concentrationconcentrated
3. customThe reaction
4. temperatureto reflux
5. additionThe addition
6. waitis complete in ˜20 min
7. waitthe mixture solidifies after ˜40 min
8. customThe oil bath is removed
9. additionn-propanol (2×25 mL) is added
10. dissolutiondissolving the remaining sodium metal
11. customThe mixture is carefully quenched through the dropwise addition of H2O (100 mL)
12. additionSaturated aq. NaCl (20 mL) is added
13. customthe layers are separated
14. dry with materialThe organic layer is dried (MgSO4)
15. filtrationfiltered
16. additiontreated with freshly prepared MeOH/HCl
17. concentrationconcentrated
18. customThe resulting solid is triturated with 30 mL EtOH
19. filtrationfiltered
20. customdried in vaccuo
21. customto afford 3.51 g as a white solid