Synthesis
4-Piperidine carboxylic acid (129 mg, 1.0 mmol) and benzoyl chloride (140 mg, 1.0 mmol) were mixed in THF (5 mL) in the presence of triethylamine (0.32 mL, 2.5 mmol). The reaction mixture was placed in a microwave reactor and stirred at 70°C, 120 W power for 15 min. Upon completion of the reaction, the reaction mixture was acidified with 1 M HCl (10 mL) and subsequently extracted with dichloromethane (3 x 25 mL). The organic layers were combined, dried with anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by fast column chromatography using hexane solution of 5% ethyl acetate and hexane solution of 80% ethyl acetate sequentially as eluent to afford 1-benzoylpiperidine-4-carboxylic acid in 94% yield as a white solid with melting point of 136-138°C. 1H NMR (400 MHz, CDCl3) δ 1.71-1.85 (m, 3H), 2.03- 2.06 (m, 1H), 2.59 (tt, 1H, J = 10.4, 4.1 Hz), 3.04-3.12 (m, 2H), 3.72-3.76 (m, 1H), 4.48-4.52 (m, 1H), 7.36-7.44 (m, 5H), 11.16 (br s, 1H).13C NMR (100 MHz. CDCl3) δ 40.4, 41.4, 46.8, 126.7, 128.3, 129.6, 135.3, 170.7, 178.3. HRMS (ESI): C13H14NO3 [M-H] Calculated value, 232.0973; measured value, 232.0979.
References
[1] Bioorganic Chemistry, 2018, vol. 80, p. 245 - 252
[2] Tetrahedron Letters, 2014, vol. 55, # 12, p. 2037 - 2039
[3] Patent: WO2016/151484, 2016, A1. Location in patent: Paragraph 0327
[4] Journal of Medicinal Chemistry, 2018, vol. 61, # 1, p. 119 - 139
[5] Patent: US5948786, 1999, A
