Water → HCID 68611056, compound

Participants

Reaction Steps

Trifluoroacetic acid (1.5 mL) and water (0.15 mL) were added to CH2Cl2 (7.5 mL). This mixture was added to 3-[4-[2-(benzyloxy)ethyl]-1-piperidinyl]-5-[[1-(tert-butoxycarbonyl)-2(R)-azetidinyl]methoxy]pyridine (260 mg, 0.54 mmol) in a 25 mL round-bottom flask with a magnetic stirrer under N2. After stirring overnight at room temperature, TLC analysis of the crude reaction mixture indicated that the starting material had disappeared. The mixture was concentrated, and the residue was purified by preparative HPLC (column: SunFire Prep C18, 150×19 mm, 5 μm particle size; UV detection at 270 nm; mobile phase: A, water with 0.05% CF3COOH; B, methanol; 40-50% B in A in 6 min, up to 100% in 1 min, back to 40% in 1 min). The eluate was partially evaporated under reduced pressure (bath 30° C.) to remove CH3OH. The residue was basified with saturated aqueous NaHCO3 solution and extracted with EtOAc. The combined organic layers were washed with brine and dried. After concentrated in vacuo, the free base (130 mg, 63%) was obtained as a yellow oil. 1H NMR (CDCl3, 300 MHz) δ 7.97 (s, 1H), 7.79 (s, 1H), 7.38-7.28 (m, 5H), 6.78 (s, 1H), 4.53 (s, 2H), 4.43-4.41 (m, 1H), 4.15-4.09 (m, 2H), 3.85-3.82 (m, 1H), 3.70-3.66 (m, 2H), 3.58-3.50 (m, 2H), 2.79-2.71 (dd, 2H, J=7.2 Hz, 2.1 Hz), 2.47-2.39 (m, 2H), 1.82-1.78 (d, 2H, J=1.2 Hz), 1.64-1.58 (m, 3H), 1.40-1.27 (m, 3H). LC-MS (ESI) m/z 382 (M+H+).

Provenance & Evidence