[Synthesis]
The general procedure for the synthesis of 1-acetyl-4-aminopiperidine hydrochloride from tert-butyl (1-methylpiperidin-4-yl)carbamate was as follows: tert-butyl 1-(1-acetylpiperidin-4-yl)carbamate (7.72 g, 44.24 mmol) was dissolved in 1,4-dioxane (100 mL) and cooled to 0 °C, followed by the dropwise addition of 1.4 M HCl of 1,4- dioxane solution (12.2 mL, 48.7 mmol). Upon completion of the dropwise addition, a white precipitate was observed to be generated and the precipitate was separated by filtration. The resulting precipitate was dissolved in methanol (100 mL), 1,4- dioxane solution (12.2 mL, 48.7 mmol) of 4.0 M HCl was added and the reaction mixture was stirred for 16 hours at room temperature. After that, a 1,4-dioxane solution (6.10 mL, 24.4 mmol) of 4.0 M HCl was added and the reaction mixture was heated to 40 °C with continuous stirring for 1.5 hours. After completion of the reaction, the volatile solvent was removed by distillation under reduced pressure and the resulting white solid was dried at high temperature. 1-Acetyl-4-aminopiperidine hydrochloride (8.60 g, purity about 90%, yield >95%) was finally obtained. The structure of the product was confirmed by 1H NMR (400 MHz, d6-DMSO): δ 8.52-8.23 (m, 3H), 4.39-4.26 (m, 1H), 3.89-3.77 (m, 1H), 3.28-3.14 (m, 1H), 3.11-3.00 (m, 1H), 2.65-2.54 (m, 1H), 1.99 (s, 3H), 1.97-1.86 (m, 2H), 1.54-1.41 (m, 1H), 1.41-1.27 (m, 1H). |