Synthesis
The general procedure for the synthesis of 1-benzylpiperidine-3-carboxylic acid from ethyl 1-benzylpiperidine-3-carboxylate was as follows: a 4N aqueous sodium hydroxide solution (15 ml) was slowly added to a mixture of tetrahydrofuran (30 ml) and 1,4-dioxane (30 ml) containing ethyl 1-benzyl-3-piperidinecarboxylate (7.00 g, 28.3 mmol). The reaction mixture was stirred at room temperature for 4 hours. Subsequently, 4N aqueous sodium hydroxide solution (15 ml) was added again and stirring was continued at room temperature overnight. After completion of the reaction, 2N hydrochloric acid (15 ml) was slowly added to neutralize the reaction solution under ice bath cooling conditions. The neutralized mixture was azeotropically dehydrated using toluene. The obtained residue was suspended in ethanol and after filtration, the filtrate was concentrated to finally obtain 1-benzyl-3-piperidine carboxylic acid (6.3 g, 100% yield).
References
[1] Patent: EP1403255, 2004, A1. Location in patent: Page 66
[2] Journal of Medicinal Chemistry, 2003, vol. 46, # 25, p. 5512 - 5532
[3] Patent: WO2008/55959, 2008, A1. Location in patent: Page/Page column 65
