Synthesis
To a stirred solution of 3-chlorosulfonylbenzoic acid (1.10 g, 5.00 mmol) in dichloromethane (DCM, 10 mL) was slowly added hexahydropyridine (piperidine, 1.49 g, 17.5 mmol) at 0 °C. The reaction mixture was continued to be stirred at 0 °C for 30 min. Upon completion of the reaction, the volatile solvent was removed by rotary evaporator under reduced pressure. The residue was treated with 1N aqueous solution of potassium bisulfate (KHSO4) to neutralize the excess piperidine. Subsequently, the aqueous phase was extracted with ethyl acetate (3 x 10 mL). The organic phases were combined and dried with anhydrous magnesium sulfate. After filtration to remove the desiccant, the filtrate was concentrated by rotary evaporator under reduced pressure to afford the white solid product 3-(piperidin-1-ylsulfonyl)benzoic acid (1.22 g, 90.4% yield). The structure of the product was confirmed by 1H NMR (d6-DMSO): δ 13.54 (1H, br s, COOH), 8.24 (1H, dt, J = 8.0, 1.4 Hz, Ar-H), 8.18 (1H, t, J = 1.8 Hz, Ar-H), 7.97 (1H, dt, J = 8.0, 1.6 Hz, Ar-H), 7.79 (1H, t, J = 7.7 Hz, Ar-H), 2.93-2.88 (4H, m, N-CH2), 1.58-1.50 (4H, m, CH2), 1.40-1.32 (2H, m, CH2).
References
[1] Patent: US2009/192195, 2009, A1. Location in patent: Page/Page column 13-14
[2] Patent: WO2016/16370, 2016, A1. Location in patent: Page/Page column 38; 39
[3] Patent: WO2009/93029, 2009, A1. Location in patent: Page/Page column 39
[4] Journal of Medicinal Chemistry, 2013, vol. 56, # 15, p. 6146 - 6155
[5] ChemMedChem, 2018, vol. 13, # 12, p. 1165 - 1171
