反应详情

With ice-cooling, 29.2 g (256 mmol) of N-ethylpiperazine and 50.0 g (256 mmol) of tert-butyl 4-oxopiperidine-1-carboxylate (corresponds to 1-Boc-4-piperidone) were initially charged in 800 ml of ethanol and 15.4 g (256 mmol) of glacial acetic acid were added. A little at a time, 16.1 g (256 mmol) of sodium acetoxyborohydride was then added to the cooled reaction mixture. Initially, a slight evolution of gas and, after ⅔ of the reducing agent had been added, foaming could be observed. The reaction mixture was stirred at room temperature overnight. For work-up, 200 ml of 2 N aqueous sodium hydroxide solution were added with cooling to the reaction solution, the solvent ethanol was distilled off and the reaction mixture which remained was diluted with water. The mixture was extracted with diethyl ether (2×) and washed with saturated sodium chloride solution (1×), the combined organic phases were dried over magnesium sulphate and filtered and the solvent was removed under reduced pressure. The desired product was obtained as a yellow oil which was subsequently chromatographed on a 4 l Nutsche filter filled with silica gel, using dichloromethane and 10% methanol as eluents. This gave a total of 40 g (135 mmol, 53%) of tert-butyl 4-(4-ethylpiperazin-1-yl)piperidine-1-carboxylate.

1. temperatureWith ice-cooling
2. additionInitially, a slight evolution of gas and, after ⅔ of the reducing agent had been added
3. temperaturewith cooling to the reaction solution
4. distillationthe solvent ethanol was distilled off
5. additionthe reaction mixture which remained was diluted with water
6. extractionThe mixture was extracted with diethyl ether (2×)
7. washwashed with saturated sodium chloride solution (1×)
8. dry with materialthe combined organic phases were dried over magnesium sulphate
9. filtrationfiltered
10. customthe solvent was removed under reduced pressure