反应详情

tert-Butyl 2-(4-nitrophenyl)morpholine-4-carboxylate (I87) (100 mg, 0.324 mmol), activated charcoal (20 mg), iron(III) chloride hexahydrate (9 mg, 10 mol %), methanol (1 mL) and hydrazine hydrate (162 mg, 1.62 mmol @50%) were refluxed together for five hours. The mixture was filtered through cotton, and the cotton washed with DCM (5 mL). The filtrate was evaporated, and redissolved in 95% ethanol (3 mL) and ethyl acetate (2 mL). A solution of ammonium chloride (173 mg. 3.24 mmol) in water (1 mL) was added, followed by indium powder (153 mg, 1.30 mmol). The mixture was refluxed for four hours then filtered. The collected solids were washed with DCM (20 mL) and the combined filtrates then diluted with water (10 mL) and saturated sodium bicarbonate (10 mL). The aqueous phase was washed with DCM (2×25 mL), the combined DCM extracts dried (phase separation filter) and evaporated. The residue was dissolved in 95% ethanol (3 mL), and treated at reflux with further indium powder (153 mg, 1.30 mmol) and ammonium chloride (173 mg. 3.24 mmol) in water (1 mL). After three hours the mixture was diluted with water (10 mL) and filtered. The collected solids were washed sequentially with ethyl acetate (25 mL) and saturated sodium bicarbonate (10 mL). The filtrate aqueous phase was separated, and washed with ethyl acetate (2×25 mL). The combined organic extracts were washed with brine (50 mL), dried and evaporated. The residue was chromatographed (12 g silica cartridge, 0-100% ethyl acetate/petroleum benzine 40-60° C.) to give the title compound (I88) (51.4 mg, 57% yield) as a yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.19-7.12 (m, 2H), 6.71-6.63 (m, 2H), 4.33-4.25 (m, 1H), 4.03-3.85 (m, 3H), 3.73-3.60 (m, 3H), 3.02 (s, 1H), 2.84 (s, 1H). LCMS Method C: rt: 4.72 min; m/z 179.1 [M-Boc+2H]+.

1. filtrationThe mixture was filtered through cotton
2. washthe cotton washed with DCM (5 mL)
3. customThe filtrate was evaporated
4. dissolutionredissolved in 95% ethanol (3 mL)
5. temperatureThe mixture was refluxed for four hours
6. filtrationthen filtered
7. washThe collected solids were washed with DCM (20 mL)
8. additionthe combined filtrates then diluted with water (10 mL) and saturated sodium bicarbonate (10 mL)
9. washThe aqueous phase was washed with DCM (2×25 mL)
10. dry with materialthe combined DCM extracts dried
11. custom(phase separation filter)
12. customevaporated
13. dissolutionThe residue was dissolved in 95% ethanol (3 mL)
14. additiontreated
15. filtrationfiltered
16. washThe collected solids were washed sequentially with ethyl acetate (25 mL) and saturated sodium bicarbonate (10 mL)
17. customThe filtrate aqueous phase was separated
18. washwashed with ethyl acetate (2×25 mL)
19. washThe combined organic extracts were washed with brine (50 mL)
20. customdried
21. customevaporated
22. customThe residue was chromatographed (12 g silica cartridge, 0-100% ethyl acetate/petroleum benzine 40-60° C.)