반응 단계
Cesium carbonate (5.34 g, 16.4 mmol) was added to a solution of 2-butyl-4-chloro-1-{[2′-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazole-5-carboxylic acid (Intermediate 4, 8.56 g, 12.6 mmol) and (1S)-1-chloroethyl (3S,3aR,6R,6aS)-6-(nitrooxy)hexahydrofuro[3,2-b]furan-3-yl carbonate (Intermediate 2, 3.75 g, 12.6 mmol) in N,N-dimethylformamide (126 mL). The mixture was heated to 70° C. for 2 hours. Water was added and the solution was extracted with ethyl acetate (2×). The combined organic layers were dried (magnesium sulfate), filtered, and concentrated in vacuo. The residue was purified by flash chromatography, eluting with 0-100% ethyl acetate in hexanes to give a yellow foam that was subsequently dissolved in methanol (106 mL). The solution was stirred at 70° C. for 2 hours and then concentrated in vacuo. The residue was purified by HPLC reverse phase (C-18), eluting with acetonitrile/water+0.1% trifluoroacetic acid to give the title compound. 1H NMR (500 MHz, CDCl3) δ 8.00 (d, J=7.5 Hz, 1H), 7.61 (t, J=7.5 Hz, 1H), 7.54 (t, J=7.5 Hz, 1H), 7.43 (d, J=8.0 Hz, 1H), 7.15 (d, J=8.0 Hz, 2H), 6.95 (d, J=8.0 Hz, 2H), 6.85 (q, J=5.5 Hz, 1H), 5.55 (d, J=16.5 Hz, 1H), 5.45 (d, J=16.5 Hz, 1H), 5.27 (td, J=5.5, 3.0 Hz, 1H), 5.03 (d, J=3.0 Hz, 1H), 4.84 (t, J=5.5 Hz, 1H), 4.39 (d, J=5.5 Hz, 1H), 4.00 (d, J=11.0 Hz, 1H), 3.95-3.88 (m, 2H), 3.78 (dd, J=11.0, 5.5 Hz, 1H), 2.66 (t, J=8.0 Hz, 2H), 1.68 (quintet, J=8.0 Hz, 2H), 1.60 (d, J=5.5 Hz, 3H), 1.36 (sextet, J=8.0 Hz, 2H), 0.89 (t, J=8.0 Hz, 3H); LC-MS: m/z 698.2 (M+H).
