Synthesis
The synthesis method of 1-Methylpiperidine-4-carboxylic acid Hydrochloride is shown below: Charge isonipecotic acid, palladium, and purified water into a reaction vessel. Heat the resulting mixture to 90 to 95° C. Charge formic acid and formaldehyde to the vessel. Cool the resulting mixture to 20 to 30° C. Filter the reaction mixture through GF/F. Wash the filter cake with purified water. Concentrate the combined filtrates to ca 2 vol at atmospheric pressure. Adjust the temperature 65 to 75° C. Charge conc—hydrochloric acid to the vessel. Charge acetonitrile to the vessel at ≧70° C. and concentrate the solution to ca 2 vol at atmospheric pressure. Charge acetonitrile to the vessel. Moreover, concentrate the solution at atmospheric pressure to ca 2 vol. Charge acetonitrile to the vessel. Moreover, concentrate the solution at atmospheric pressure to ca 3 vol. Check the water content by KF analysis of the supernatant liquors using AX reagent. Cool the reaction mixture to 20 to 25° C. Stir the reaction mixture for 1 to 2 hours. Filter the reaction mixture. Wash the filter cake with acetonitrile. Dry the product up to 50° C. until ≦0.5% w/w by LOD and ≦0.2% w/w water.
References
[1] Journal of Medicinal Chemistry, 1988, vol. 31, # 4, p. 807 - 814
[2] Patent: WO2011/123654, 2011, A1. Location in patent: Page/Page column 29-30
[3] Patent: WO2010/83384, 2010, A2. Location in patent: Page/Page column 61
