General procedure for the synthesis of 3-(1-methylpiperidin-4-yl)-1-propanol from 1-N-BOC-4-piperidinepropionic acid:
A. Synthesis of 3-(1-methylpiperidin-4-yl)-propan-1-ol. To a tetrahydrofuran (THF) solution (40 mmol) of 1N lithium aluminum hydride, a THF solution (30 mL) of N-BOC-4-piperidinepropionic acid (3.0 g, 11.6 mmol) was added slowly and dropwise under reflux conditions. The reaction mixture was heated to reflux for 3 hours and then cooled to room temperature. The mixture was further cooled to 0 °C, water (1.5 mL) was slowly added and the reaction mixture was warmed to room temperature within 15 minutes. The mixture was again cooled to 0°C and 10% sodium hydroxide solution (1.5 mL) was slowly added. After warming to room temperature within 15 minutes, the mixture was again cooled to 0°C and additional water (4.5 mL) was added. The resulting mixture was slowly warmed to room temperature over 18 hours and subsequently filtered through a diatomaceous earth pad. The filtrate was concentrated under reduced pressure and the residue was purified by method 2 to give 1.9 g (100% yield) of 3-(1-methylpiperidin-4-yl)-propan-1-ol as a yellow oil. Mass spectrum (electrospray): calculated mass of C9H19NO, 157.15; measured value: 157.15. m/z found, 158.1 [M+H]+. 1H NMR (400MHz, CD3OD): δ 3.45-3.41(m, 2H), 2.77-2.74(m, 2H), 1.89-1.85(m, 2H), 1.64 -1.61(m, 2H), 1.47-1.43(m, 2H), 1.21-1.12(m, 5H).
