[Synthesis]
The general procedure for the synthesis of 1-methyl-4-piperidinemethanol from ethyl N-methyl-4-piperidinecarboxylate is as follows:
Synthesis of Example 23 (1-methylpiperidin-4-yl)methanol (22): a solution of ethyl N-methyl-4-piperidinecarboxylate (21, 10.1 g, 59.0 mmol) in ethyl ether (Et2O, 40 mL) was slowly added dropwise to an ethyl ether suspension of lithium aluminum hydride (LiAlH4, 2.46 g, 64.9 mmol). The reaction system was cooled at 0 °C, followed by the addition of ether (200 mL). The reaction mixture was gradually warmed to room temperature and stirred continuously at this temperature for 4 hours. Upon completion of the reaction, the reaction was quenched by the slow addition of water (10 mL) and stirring was continued for 30 minutes. The resulting white precipitate was separated by filtration and washed well with ether (250 mL). After concentration under reduced pressure to remove the solvent, the oily product obtained was purified by distillation under reduced pressure (boiling point 108 °C, 14 mbar) to give the target compound 22 (6.40 g, 84% yield) as a colorless oil.
-Thin layer chromatography (TLC) analysis: Rf = 0.53 (Expanding agent: dichloromethane/methanol = 5:1 with 5% triethylamine, phosphomolybdic acid color development: dark blue spots).
-Nuclear magnetic resonance hydrogen spectrum (1H NMR, 300MHz, CDCl3): δ= 1.28 (dq, J = 12.2, 3.7Hz, 2H, 3-Hax, 5-Hax), 1.38-1.55 (m, 1H, 4-H), 1.68-1.79 (m, 2H, 3-Heq, 5-Heq), 1.93 (dt, J = 11.8, 2.3Hz, 2H, 2H, 4-H). 2.3 Hz, 2H, 2-Hax, 6-Hax), 2.26 (s, 3H, NMe), 2.82-2.92 (m, 2H, 2-Heq, 6-Heq), 3.12 (sbr, 1H, OH), 3.46 (d, J = 6.4 Hz, 2H, CH2OH) ppm.
-Nuclear magnetic resonance carbon spectrum (13C NMR, 75.5 MHz, CDCl3): δ= 28.8 (C-3, C-5), 37.9 (C-4), 46.3 (NMe), 55.5 (C-2, C-6), 67.4 (CH2OH) ppm.
-Mass spectrum (MS, 70eV, EI): m/z (%) = 129 (55) [M]+, 128 (100) [M-H]+, 112 (10) [M-OH]+, 98 (21) [M-CH2OH]+.
-Molecular formula: C7H15NO (molecular weight: 129.20). |