Sodium Bicarbonate → 4-{4-[(1-isopropylpiperidin-4-yl)oxy]phenyl}tetrahydro-2H-pyran-4-carboxamide

Participants

Reaction Steps

4-[4-(1-Isopropylpiperidin-4-yloxy)phenyl]tetrahydropyran-4-carbonitrile (50 mg, 0.152 mmol) was combined with boron trifluoride-acetic acid complex (500 μL, 3.6 mmol) and stirred at ambient temperature for 18 hours, followed by 65° C. for 3 hours. The reaction mixture was allowed to cool and then basified with saturated NaHCO3 solution (15 mL). The product was extracted with dichloromethane (2×35 mL). The combined organic extracts were dried using Na2SO4 filtered and concentrated in vacuo. The compound was purified by column chromatography on silica gel (15 g), eluting with dichloromethane:methanol:ammonia, (96:4:0.4) to dichloromethane:methanol:ammonia, (90:10:1) to give the title compound as a white solid (22 mg, 42%). 1H NMR (400 MHz, CD3OD) δ7.3 (d, 2H), 6.9 (d, 2H), 4.4 (m, 1H), 3.8 (m, 2H), 3.65 (m, 2H), 2.78-2.85 (m, 3H), 2.5 (m, 2H), 2.4 (d, 2H), 1.95-2.08 (m, 4H), 1.8 (m, 2H), 1.1 (d, 6H)

Provenance & Evidence