反应详情

Trans {1-[2-(4-amino-cyclohexyl)-ethyl]-piperidin-4-yl}-(4-fluoro-phenyl)-methanone (example 1, intermediate F) (80 mg, 0.24 mmol) was dissolved in 1.5 ml dichloromethane and N-ethyldiisopropylamine (0.33 ml, 1.93 mmol) was added. Triphosgene (79 mg, 0.27 mmol) was added carefully and the solution stirred for 30 minutes at room temperature. Indoline (32 mg, 0.27 mmol) was added and stirred for 30 minutes at room temperature. The reaction mixture was extracted with sat. NaHCO3-solution and dichloromethane. The organic extracts were washed with brine, dried with sodium sulfate, filtered and evaporated. The crude product was purified by flash chromatography on silica gel (dichloromethane/methanol 100:0->90:10 gradient). The desired compound was obtained as a white solid (51 mg, 44%), MS: m/e=478.2 (M+H+).

1. stirringstirred for 30 minutes at room temperature
2. extractionThe reaction mixture was extracted with sat. NaHCO3-solution and dichloromethane
3. washThe organic extracts were washed with brine
4. dry with materialdried with sodium sulfate
5. filtrationfiltered
6. customevaporated
7. customThe crude product was purified by flash chromatography on silica gel (dichloromethane/methanol 100:0->90:10 gradient)