N[CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.[BH3-][C:16]#[N:17].[Na+].[CH3:19]C(O)=O.C=O.C(Cl)[Cl:26]>CO>[ClH:26].[ClH:26].[CH2:8]([N:5]1[CH2:6][CH2:7][CH:2]([N:17]([CH3:16])[CH3:19])[CH2:3][CH2:4]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1To a mixture of 4-amino-1-benzyl piperidine (5.0 g, 26 mmol), NaBH3CN (3.3 g, 53 mmol), AcOH (7.5 ml, 132 mmol) in 130 ml MeOH at 0° C. under nitrogen was added formaldehyde (37 wt % in water, 5.3 mL) as a solution in 15 ml MeOH slowly dropwise via a pressure-equalized addition funnel over 15 min. The resulting clear solution was allowed to warm to room temperature and was allowed to stir for approximately 60 h. The reaction was quenched by the addition of 20 ml saturated aqueous potassium carbonate. The mixture was concentrated in vacuo, and water and EtOAc was added. The organic layer was removed, and the aqueous layer was extracted twice with EtOAc. The combined organic layers were dried with Na2SO4, filtered, and concentrated to give a cloudy oil, which was dissolved in methylene chloride and filtered through a fritted funnel. The solvent was removed to give a waxy solid, which was purified by silica gel chromatography (MC/MeOH/conc. NH4OH). The resulting material was dissolved in diethyl ether, cooled to 0° C. and treated with 20 ml 4N HCl in dioxane. The solvent was removed in vacuo to give the desired product as a white solid. MS (m/z): 219.1 (M+H)+. Calc'd for C14H22N2: 218.34.
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