反应详情

Add potassium hydroxide (170 mg, 3.03 mmol) in one portion to a solution of 3-tert-butoxycarbonyl-7-chloro-6-dimethylcarbamoylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepine (187 mg, 0.49 mmol) in methanol (10 mL). Heat the reaction at reflux under nitrogen overnight. Then add further portion of KOH (867 mg, 15.45 mmol) and heat at reflux for 3 h. Then cool to room temperature and add 1-(3-bromo-propyl)-1,3-dihydro-3,3-dimethyl-indol-2-one (274 mg, 0.97 mmol, prepared by following the procedure described in Perkin 1 2000, 769-774). Stir the reaction at room temperature overnight. Remove solvents in vacuo, add water and extract with diethyl ether (2×50 mL). Combine the organic extracts, wash with water (2×50 mL) and brine (50 mL). Dry over MgSO4 and concentrate in vacuo. Purify by chromatography on silica gel eluting with isohexane/EtOAc (1:0 to 1:1 gradient over 40 min) to give 3-tert-butoxycarbonyl-7-chloro-6-[3-(3,3-dimethyl-2-oxo-2,3-dihydro-indol-1-yl)-propylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a colourless oil (330 mg), 50% contaminated with 1-(3-methoxypropyl)-1,3-dihydro-3,3-dimethyl-indol-2-one. MS (ES+) m/z: 537 (M+Na)+.

1. temperatureHeat
2. customthe reaction
3. temperatureat reflux under nitrogen overnight
4. temperatureheat
5. temperatureat reflux for 3 h
6. customprepared
7. customthe reaction at room temperature overnight
8. extractionextract with diethyl ether (2×50 mL)
9. washCombine the organic extracts, wash with water (2×50 mL) and brine (50 mL)
10. dry with materialDry over MgSO4
11. concentrationconcentrate in vacuo
12. customPurify by chromatography on silica gel eluting with isohexane/EtOAc (1:0 to 1:1 gradient over 40 min)