Synthesis
General procedure for the synthesis of N-BOC-3-piperidinecarboxamide from 1-BOC-piperidine-3-carboxylic acid: To a chloroform solution (10 mL) of 1-Boc-piperidine-3-carboxylic acid (1.58 g, 6.89 mmol) was added drop-wise at 0 °C and under nitrogen protection, triethylamine (0.96 mL, 6.89 mmol) and ethyl chloroformate (0.69 mL, 7.23 mmol). The reaction mixture was stirred at 0°C for 10 min and then ammonia (gas) was passed for 1 hr. Subsequently, the reaction mixture was warmed to room temperature and stirring was continued for 3 hours. Upon completion of the reaction, 5% aqueous sodium bicarbonate solution was added to separate the organic and aqueous phases. The organic layer was dried with anhydrous sodium sulfate and concentrated under reduced pressure to give the crude N-BOC-3-piperidinecarboxamide, which can be used in subsequent reactions without further purification. Yield: quantitative; LCMS (retention time): 3.31 min (Method A); mass spectrometry (electrospray positive ionization mode) showed m/z: 229.0 ([M+H]+).
References
[1] Patent: WO2006/123257, 2006, A2. Location in patent: Page/Page column 34
[2] Patent: US8080566, 2011, B1. Location in patent: Page/Page column 37-38
[3] European Journal of Medicinal Chemistry, 1984, vol. 19, # 2, p. 181 - 186
[4] Journal of Medicinal Chemistry, 2007, vol. 50, # 9, p. 2225 - 2239
[5] Patent: WO2014/149164, 2014, A1. Location in patent: Paragraph 00605
