Reaction Steps
A mixture of CF3COOH, H2O, and CH2Cl2 (10:1:50, 6.1 mL) was added to a 15 mL round-bottom flask containing 3-[5-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]-3-pyridyl]-3-azabicyclo[3.2.1]octane (182 mg, 446 μmol). 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 with an oil pump (40° C.). The residue was purified by preparative HPLC (Supelco Discovery C18, 250×21.2 mm, 5 μm particle size, UV detection at 270 nm, flow rate 4.9 mL/min, 8% CH3CN in water for 10 min followed by gradient from 8% to 25% for 35 min, from 25% to 100% for another 35 min, then 100% CH3CN for 40 min, both solvents containing 0.1 vol % CF3COOH; tR 48.8-59.5 min) to give the yellow tifluoroacetate (260 mg, 94%). 1H NMR (CD3OD, 500 MHz) δ 8.00 (d, 1H, J=2.2 Hz), 7.89 (d, 1H, J=1.9 Hz), 7.41 (d, 1H, J=2.2 Hz), 4.68 (dt, 1H, J1=10.6 Hz, J2=3.2 Hz), 4.38-4.32 (m, 1H), 4.17-4.07 (m, 1H), 3.64 (d, 2H, J=11.2 Hz), 3.46-3.39 (m, 2H), 3.06 (d, 2H, J=11.2 Hz), 2.49 (s, br, 2H), 2.36-2.27 (m, 1H), 2.24-2.16 (m, 1H), 2.16-2.08 (m, 1H), 2.01-1.91 (m, 1H), 1.88-1.81 (m, 2H), 1.72 (s, br, 2H), 1.65 (d, 2H, J=7.7 Hz); MS (EI) m/z 287 (M+ of free base, 0.8%). Anal. Calcd. for C17H25N3O.2.93CF3COOH (FW 621.5): C, 44.18; H, 4.53; N, 6.76; F, 26.87. Found: C, 44.20; H, 4.44; N, 6.73; F, 26.89.
