1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinylmethyl methanesulfonate (82.3 g, 271 mmol) and 5-hydroxy-2-(4-methylsulfonylphenyl)pyridine (71.0 g, 285 mmol) were added with powdered potassium carbonate (118 g, 855 mmol) and N,N-dimethylformamide ( 750 mL), and the reaction was mechanically stirred at 80 °C for 20 h under nitrogen protection. After completion of the reaction, it was cooled to room temperature, poured into ice water (3 L) and left to stand for 1 hour. The solid product was collected by filtration, washed with water (2 x 500 mL) and air dried. The dried solid was dissolved in a solvent mixture of dichloromethane (300 mL) and methanol (500 mL). The dichloromethane was slowly evaporated by rotary evaporator at 55°C. The remaining methanol solution was allowed to stand at room temperature for 16 hours to induce crystallization. The crystalline solid was obtained by filtration, washed with cold methanol and dried under vacuum at 60 °C for 18 h. The target compound 3-isopropyl-5-(4-(((6-(4-(4-(methylsulfonyl)phenyl)pyridin-3-yl)oxy)methyl)piperidin-1-yl)-1,2,4-oxadiazole (105.7 g, 84% yield) was obtained as a light tan solid.1H NMR (400 MHz. CDCl3): δ 8.41 (d, 1H, J=2.8 Hz), 8.13 (d, 2H, J=8.6 Hz), 8.01 (d, 2H, J=8.6 Hz), 7.74 (d, 1H, J=8.7 Hz), 7.29 (dd, 1H, Ja=8.7 Hz, Jb=3.0 Hz), 4.24 (d, 2H, J=13.1 Hz), 3.95 (d, 2H, J=6.2 Hz), 3.17-3.04 (m, 5H), 2.94-2.84 (m, 1H), 2.11 (bs, 1H), 1.97 (d, 2H, J=12.6 Hz), 1.54-1.42 (m, 2H), 1.29 (d, 6H, J=7.0 Hz); LRMS (ESI ), m/z 457 (M+H).
