Synthesis
The general procedure for the synthesis of N-Boc-4-cyanopiperidine from tert-butyl 4-carbamoylpiperidine-1-carboxylate is as follows: to a solution of ethyl acetate (EtOAc, 1 mL, 1 M) containing an aldoxime or amide (1.0 mmol) and triethylamine (Et3N, 1.5 mmol) was added batchwise to XtalFluor-E (1.1 mmol) at room temperature. ). The reaction mixture was stirred at room temperature for 1 hour. Subsequently, the reaction was quenched with saturated sodium bicarbonate (NaHCO3) solution and extracted with aqueous sodium carbonate (Na2CO3) and dichloromethane (CH2Cl2, 2 × 10 mL). The combined organic layers were washed sequentially with water and brine, dried over anhydrous magnesium sulfate (MgSO4) and concentrated under reduced pressure to give the crude product. If necessary, the crude product can be purified by fast column chromatography.
References
[1] Synthesis (Germany), 2015, vol. 47, # 23, p. 3758 - 3766
[2] Patent: WO2004/2483, 2004, A1. Location in patent: Page/Page column 21-22; 39-40
[3] Chemistry of Heterocyclic Compounds, 2009, vol. 45, # 12, p. 1503 - 1507
[4] European Journal of Medicinal Chemistry, 1984, vol. 19, # 2, p. 181 - 186
[5] Chemical and Pharmaceutical Bulletin, 2001, vol. 49, # 7, p. 822 - 829
