A mixture of CF3COOH, H2O, and CH2Cl2 (10:1:50, 2.44 mL) was added to a 10 mL round-bottom flask containing 3-[2-[5-[[1-(tert-butoxycarbonyl)-2(S)-azetidinyl]methoxy]-3-pyridyl]phenyl]-1-propanol (99.5 mg, 0.25 mmol). The flask was capped with a glass stopper, and the reactants were stirred at room temperature for 14 h. The reaction mixture was concentrated with a rotary evaporator (bath up to 35° C.) and was further dried on an oil pump (35° C.). The residue was dissolved in water (1 mL), and the aqueous solution was lyophilized. The resulting oil was purified by preparative HPLC in two portions (Supelco Discovery C18, 250×21.2 mm, 5 μm particle size, UV detection at 270 nm, flow rate 12.5 mL/min, gradient from 8% to 25% CH3CN in water within 20 min, from 25% to 100% in another 20 min, then 100% CH3CN for 20 min, both solvents containing 0.1 vol % CF3COOH; tR 19.6-23.7 min). Partial evaporation to remove CH3CN, followed by lyophilization, gave the product as a yellowish oil (121 mg, 82%). 1H NMR (CD3OD, 500 MHz) δ 8.85 (s, 1H), 8.41 (s, 1H), 7.93 (s, 1H), 7.45 (d, 2H, J=4.6 Hz), 7.38-7.33 (m, 1H), 7.29 (d, 1H, J=7.6 Hz), 4.98-4.95 (m, 1H), 4.61-4.52 (m, 2H), 4.21-4.09 (m, 2H), 3.48 (t, 2H, J=6.2 Hz), 2.72 (t, 4H, J=6.2 Hz), 1.78-1.69 (m, 2H). Anal. Calcd. for C18H22N2O2.2.41CF3COOH.1.04H2O (FW 591.9): C, 46.30; H, 4.51; N, 4.73; F, 23.21. Found: C, 46.31; H, 4.40; N, 4.71; F 23.18.
