Synthesis
To a solution of tert-butyl (1-benzylpiperidin-3-yl)methylcarbamate (2.05 g, 6.74 mmol, 1.0 equiv) in methanol (40 mL) was added 10% Pd(OH)2/C (0.21 g, 10 wt%). Cyclohexene (6.80 mL, 67.40 mmol, 10.0 eq.) was added to the reaction system under argon protection. The resulting suspension was refluxed under argon atmosphere for 20 hours. Upon completion of the reaction, it was filtered through a Celite pad (Celite 577 fine) and the filtrate was concentrated under reduced pressure to give the crude product. The crude product was purified by fast column chromatography with the eluent of dichloromethane/methanol/triethylamine (3:1:0.1, v/v/v) to afford 1.31 g of the target compound 3-Boc-aminomethylpiperidine as a colorless viscous oil. Yield: 91%; Thin Layer Chromatography Rf = 0.33 (dichloromethane/methanol/triethylamine = 3:1:0.1); 1H NMR (400 MHz, CDCl3) δ: 1.08 (qd, J = 11.2, 4.0 Hz, 1H, CH2CHAHBCH), 1.42 (s, 9H, 3 x CH3), 1.45-1.52 (m, 1H. CHAHBCH2CH), 1.58-1.70 (m, 2H, CHAHBCHAHBCH), 1.76-1.82 (m, 1H, CH), 2.32 (t, J = 11.2 Hz, 1H, NHCHAHBCH), 2.52-2.60 (m, 2H, CH2CHAHBNH), 2.97-3.03 (m, 3H, CH2NHCOHBCH), 2.97-3.03 (m, 3H, CH2NHCOHBCH), 2.97-3.03 (m, 3H, CH2NHCO 3H, CH2NHCO + CH2CHAHBNH), 3.06 (dd, J = 11.6, 3.2 Hz, 1H, NHCHAHBCH), 4.63 (br s, 1H, NHCO); 13C NMR (100 MHz, CDCl3) δ: 24.99, 27.97, 28.27, 36.86, 43.74, 45.90, 49.54, 78.28, 155.86; ESI-HRMS m/z calculated C11H23N2O2 [M+H]+ 215.1760, measured 215.1763; IR (KBr) υ: 3385, 2978, 2934, 1685, 1528, 1458, 1367, 1272, 1254, 1174, 1009 cm-1 1174, 1009 cm-1.
References
[1] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 15, p. 4442 - 4452
[2] Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 2, p. 633 - 645
[3] Journal of Medicinal Chemistry, 2018, vol. 61, # 1, p. 119 - 139
