tert-butyl 2-piperidin-4-ylpyrrolidine-1-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of tert-butyl 2-(piperidin-4-yl)pyrrolidine-1-carboxylate (400 mg, 1.57 mmol) in dry DMF (2.0 mL) at 0° C., was added NaH (132 mg, 3.30 mmol, 60% in mineral oil) in small portions. The reaction mixture was then warmed to room temperature with stirring for another 1 h. 2-iodopropane (2.0 mL) was added. The resulting mixture was stirred at room temperature for 24 h and then poured into the ice-water (20 mL). The resultant mixture was extracted with EtOAc (2×50 mL). The combined organic layers were dried over Na2SO4 and evaporated to dryness. The residue was purified by silica gel chromatography using 5-10% MeOH in DCM as eluant to afford the desired product (302 mg, 65% yield). LCMS m/z [M+H]+ 297.2. The resulting mixture was stirred at room temperature for 24 h The resultant mixture was extracted with EtOAc (2×50 mL) The combined organic layers were dried over Na2SO4 evaporated to dryness The residue was purified by silica gel chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of tert-butyl 2-(piperidin-4-yl)pyrrolidine-1-carboxylate (400 mg, 1.57 mmol) in dry DMF (2.0 mL) at 0° C., was added NaH (132 mg, 3.30 mmol, 60% in mineral oil) in small portion. The reaction mixture was then warmed to room temperature with stirring for another 1 h. 2-iodopropane (2.0 mL) was added. The resulting mixture was stirred at room temperature for 24 h and then poured into the ice-water (20 mL). The resultant mixture was extracted with EtOAc (2×50 mL). The combined organic layers were dried over Na2SO4 and evaporated to dryness. The residue was purified by silica gel chromatography eluting with a 5-10% gradient of MeOH in DCM to afford tert-butyl 2-(1-isopropylpiperidin-4-yl)pyrrolidine-1-carboxylate (302 mg, 65% yield). A solution of tert-butyl 2-(1-isopropylpiperidin-4-yl)pyrrolidine-1-carboxylate (302 mg, 1.02 mmol) in sat. HCl/dioxane (5 mL) was stirred at room temperature for 8 h. After removal of the solvent, 1-isopropyl-4-(pyrrolidin-2-yl)piperidine hydrochloride (232 mg, 100% yield) as yellow solid was obtained. LCMS (ESI) m/z: 197.2 [M+H+]. The resulting mixture was stirred at room temperature for 24 h The resultant mixture was extracted with EtOAc (2×50 mL) The combined organic layers were dried over Na2SO4 evaporated to dryness The residue was purified by silica gel chromatography eluting with a 5-10% gradient of MeOH in DCM