反应详情

In 1 ml of dichloromethane, 135.8 mg (0.775 mmol) of Boc-aminopropanol was dissolved, 4 ml dichloromethane solution of 229.6 mg (0.775 mmol) of diclofenac (manufactured by Wako Pure Chemical Industries), 1 ml dichloromethane solution of 18.9 mg (0.155 mmol) DMAP and 0.5 ml of DMF were added thereto in this order, and 2 ml dichloromethane solution of 191.4 mg (0.998 mmol) of WSCI.HCl was added thereto under ice-cooling, followed by stirring for 7 hours while gradually returning to room temperature. The reaction solution was again ice-cooled, and, as an additional operation, 1 ml dichloromethane solution of 91.9 mg (0.310 mmol) of diclofenac, 7.5 mg (0.061 mmol) of DMAP and 1 ml dichloromethane solution of 70.9 mg (0.370 mmol) of WSCI.HCl were added thereto in this order, followed by stirring while gradually returning to room temperature. This additional operation was carried out 5 times. Ethyl acetate was added thereto, followed by separation by washing twice with 5% aqueous citric acid solution, twice with 5% aqueous sodium hydrogen carbonate solution and with saturated brine consecutively. After dehydration with sodium sulfate, ethyl acetate was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give 280.2 mg (80%) of the titled compound. The structure was identified by 1H-NMR.

1. temperatureunder ice-cooling
2. customwhile gradually returning to room temperature
3. temperaturecooled
4. stirringby stirring
5. customwhile gradually returning to room temperature
6. customfollowed by separation
7. washby washing twice with 5% aqueous citric acid solution, twice with 5% aqueous sodium hydrogen carbonate solution and with saturated brine consecutively
8. customAfter dehydration with sodium sulfate, ethyl acetate was evaporated under reduced pressure
9. customThe resulting residue was purified by silica gel column chromatography