General procedure for the synthesis of 4-piperidinylpiperidine from hexahydropyridine and N-tert-butoxycarbonyl-4-piperidone: hexahydropyridine (1.549 g, 18.19 mmol), sodium triacetoxyborohydride (3.85 g, 19.2 mmol) and acetic acid (0.0910 g, 1.52 mmol) were added to a solution of 1-tert-butoxycarbonyl-4-piperidone (3.02 g , 15.2 mmol) in a solution of dichloromethane (25.0 mL). The reaction mixture was stirred at room temperature for 16 hours at 0 °C. Upon completion of the reaction, the reaction solution was cooled to 0 °C, the reaction was quenched by the addition of saturated aqueous sodium bicarbonate solution and extracted with dichloromethane. The organic layers were combined, dried with anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue was dissolved in 1.0 N hydrochloric acid and extracted with ethyl acetate. The aqueous phase was alkalized with 48% aqueous sodium hydroxide and extracted again with dichloromethane. The organic layer was dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue was dissolved in methanol (25.0 mL), concentrated hydrochloric acid (5.0 mL) was added and stirred at 40°C for 12 hours. After the reaction solution was concentrated and dried, the residue was dissolved in distilled water, alkalized with 48% aqueous sodium hydroxide and extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 4-(piperidin-1-yl)piperidine (2.04 g, 12.1 mmol, 80% yield) as a white solid.
