反应详情

To a solution of (R)-4-(4-((4′-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoic acid (INTERMEDIATE 40, 88 mg, 0.20 mmol), EDC (77 mg, 0.40 mmol), and DMAP (49 mg, 0.40 mmol), triethylamine (28 μl, 0.20 mmol) in 5 ml of DCM was added (R)-di-tert-butyl 2-(ethyl(4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butyl)amino)ethyl phosphate (INTERMEDIATE 50, 150 mg, 0.20 mmol). The mixture was stirred at r.t overnight. The reaction solution was diluted with DCM (20 ml) and washed with water (30 ml). The aqueous layer was extracted with DCM (30 ml) and the combined organic layers were dried over sodium sulfate, and concentrated in vacuo to an oil. This material was purified by column chromatography (ISCO, 0→100% EtOAc/hexane followed by 0→10% MeOH/EtOAc) to provide the title compound (137 mg, yield: 59%).

1. washwashed with water (30 ml)
2. extractionThe aqueous layer was extracted with DCM (30 ml)
3. dry with materialthe combined organic layers were dried over sodium sulfate
4. concentrationconcentrated in vacuo to an oil
5. customThis material was purified by column chromatography (ISCO, 0→100% EtOAc/hexane followed by 0→10% MeOH/EtOAc)