反应详情

6 N NaOH (10 mL), TsCl (0.48 g, 2.5 mmol) and (Bu4NH)2SO4 (50% solution in water, 0.17 mL) were added to a solution of tert-butyl 8-bromo-3,4,5,6-tetrahydroazepino[4,3-b]indole-2(1H)-carboxylate (0.76 g, 2.1 mmol) in toluene (17 mL), and the resulting solution was stirred for 18 h. Additional TsCl (55 mg, 0.29 mmol) was added, and the reaction was stirred for 18 h. The solution was partitioned with H2O and the resulting layers were separated. The aqueous phase was extracted with EtOAc (2×20 mL). The combined organic extracts were washed with brine (25 mL), dried over Na2SO4 and concentrated to dryness under reduced pressure. Flash chromatography (40 g ISCO hexanes/EtOAC, 90:10 for 2 column volumes, increased to 50:50 over 12 column volumes and held for 4 column volumes) provided the title compound (0.54 g, 50%) as a white foam: 1H NMR (500 MHz, DMSO-d6) δ 8.24-8.20 (m, 1H), 7.64 (d, J=8.0 Hz, 2H), 7.51 (d, J=8.5 Hz, 1H), 7.46 (dd, J=8.5, 1.5 Hz, 1H), 7.37 (d, J=8.0 Hz, 2H) 4.44-4.40 (m, 2H), 3.56 (t, J=5.5 Hz, 2H), 3.20-3.18 (m, 2H), 2.31 (s, 3H), 1.86-1.84 (m, 2H), 1.29-1.03 (m, 9H).

1. stirringthe reaction was stirred for 18 h
2. customThe solution was partitioned with H2O
3. customthe resulting layers were separated
4. extractionThe aqueous phase was extracted with EtOAc (2×20 mL)
5. washThe combined organic extracts were washed with brine (25 mL)
6. dry with materialdried over Na2SO4
7. concentrationconcentrated to dryness under reduced pressure
8. temperatureFlash chromatography (40 g ISCO hexanes/EtOAC, 90:10 for 2 column volumes, increased to 50:50 over 12 column volumes and held for 4 column volumes)