反应详情

Combine 2-[1-(3,4,5-trimethoxy-benzoyl)-3-(3,4-difluoro-phenyl)-pyrrolidin-3-yl]-ethyl-methanesulfonate (prepared from (-)-2-[3-(3,4-difluoro-phenyl)-pyrrolidin-3-yl]-ethanol (R,R)-di-p-anisoyltartaric acid salt)(0.6 g, 1.2 mmol), potassium carbonate (0.46 g, 3.4 mmol), and 4-(pyridin-3-yl)-piperidine-4-carboxylic acid amide in tetrahydrofuran (6 mL)/ water (2 mL). Heat to reflux. After 64 hours, evaporate the reaction mixture in vacuo to remove most of the tetrahydrofuran and combine with dichloromethane. Extract with a saturated aqueous solution of sodium bicarbonate. Dry the organic layer over MgSO4, filter, and concentrate in vacuo to give a residue. Chromatograph the residue on silica gel eluting sequentially with 1% methanol/dichloromethane, 3% methanol/dichloromethane, 5% methanol/dichloromethane, dichloromethane/methanol/concentrated ammonia (464/35/2.5) and then, dichloromethane/methanol/concentrated ammonia (450/50/2.5) to give the title compound: Rf =0.17 (silica gel, dichloromethane/methanol/concentrated ammonia 9/1/0.05).

1. temperatureHeat to reflux
2. customevaporate the reaction mixture in vacuo
3. customto remove most of the tetrahydrofuran
4. extractionExtract with a saturated aqueous solution of sodium bicarbonate
5. dry with materialDry the organic layer over MgSO4
6. filtrationfilter
7. concentrationconcentrate in vacuo
8. customto give a residue