Dimethylformamide → 6-(4-hydroxypiperidin-1-yl)pyridine-3-carbonitrile

Participants

Reaction Conditions

Reaction Steps

To a N,N-dimethylformamide (100 mL) solution of 2-chloro-5-cyanopyridine (36.2 g, 262 mmol) and 4-hydroxypiperidine (27.9 g, 275 mmol) was added potassium carbonate (40.1 g, 290 mmol). The reaction mixture was heated to 100° C. and stirred for 3 hours. It was cooled to room temperature, diluted with water (400 mL), and extracted with dichloromethane (3×250 mL). The combined organic extracts were washed with brine, dried (magnesium sulfate), and concentrated in vacuo to afford the title compound as a solid. This crude product was used in the subsequent step without further purification. 1H NMR (500 MHz, CDCl3) δ 8.39 (d, J=2.3 Hz, 1H), 7.58 (dd, J=9.1, 2.4 Hz, 1H), 6.62 (d, J=9.1 Hz, 1H), 4.10 (dt, J=13.6, 5.0 Hz, 2H), 4.01 (tt, J=8.3, 3.9 Hz, 1H), 3.37 (ddd, J=13.6, 9.2, 3.4 Hz, 2H), 2.61 (s, 1H), 1.99-1.92 (m, 2H), 1.62-1.53 (m, 2H); LC-MS: m/z 204.2 (M+H).

Provenance & Evidence