Compound 104

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Compound data: NMR

Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

Following GP2 outlined for compound 45, in 1,1,1,3,3,3-hexafluoro-i-propanol (HFIP) at 0 °C, but using 1.0 equiv. of (S)-((1S,2R,4S,5R)-5-ethylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methanol (as solution in HFIP 0.5 mL), 2.0 equiv. of azetidine hydrochloride, 2.0 equiv.of NCS, 2.0 of equiv of N,N-diisopropylehtylamine and 8.0 equiv. of HClO₄, (S)-((1S,2R,4S,5R)-5-ethylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methanol (32.6 mg, 0.1 mmol) gave 104 (13 mg, 34%) as a wax. R_f 0.19 [EtOAc–MeOH–AcOH (8:1:0.5)]; FT-IR ν_max (film)/cm^–1 2978, 2823, 1583, 1546, 1427, 1274, 1212, 1173, 1031; ¹H NMR (400 MHz, CDCl₃) δ 8.65 (1H, d, J = 4.5 Hz), 7.95 (1H, d, J = 9.3 Hz), 7.77 (1H, d, J = 4.4 Hz), 7.44 (1H, d, J = 9,3 Hz), 7.03 (1H, br s), 6.04 (1H, br s), 4.72 (1H, br s), 4.15 (1H, br td, J = 9.7, 3.1 Hz), 4.10–4.03 (1H, m), 4.02 (3H, s), 3.78–3.68 (2H, m), 3.55–3.39 (1H, m), 3.43 (1H, br t, J = 10.6 Hz), 3.36 (1H, dd, J = 13.0, 10.1 Hz), 3.18 (1H, dt, J = 12.6, 9.4 Hz), 2.61–2.45 (1H, m), 2.29–2.19 (1H, m), 2.06 (1H, br t, J = 12.3 Hz), 1.88 (1H, br s), 1.84–1.76 (1H, m), 1.76–1.68 (2H, m), 1.59–1.45 (3H, m), 0.88 (3H, t, J = 6.9 Hz); ¹³C NMR (101 MHz, CDCl₃) δ 157.6, 147.6, 145.0, 144.6, 131.8, 130.1, 125.8, 120.9, 116.7, 68.6, 60.9, 56.2, 51.2, 49.3, 35.4, 30.9, 25.4, 24.2, 23.9, 18.9, 16.8, 11.6; HRMS (APCI): Found MH⁺ 382.2487, C₂₃H₃₂N₃O₂ requires 382.2489.