反应详情

温度

40 °C

A mixture of 2-ethoxy-1-{[2′-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylic acid (2180 mg, 3.19 mmol), cesium carbonate (2150 mg, 6.60 mmol), and tetrabutylammonium hydrogen sulfate (538 mg, 1.59 mmol) was charged with a N,N-dimethylformamide (10 mL) solution of 1-chloroethyl (1R,3S,4S)-3-methoxy-4-(nitrooxy)cyclopentanecarboxylate (intermediate 2, 834 mg, 3.11 mmol). The reaction mixture was heated at 40° C. for 16 hours, and the reaction mixture was purified by column chromatography, eluting with 10/90→70/30 ethyl acetate/hexanes to give the title compound as a white solid. 1H NMR (500 MHz, CDCl3) δ 1.36 (d, J=5.5 Hz, 3H, D1), 1.36 (d, J=5.5 Hz, 3H, D2), 1.41 (t, J=7.1 Hz, 3H), 1.94-2.05 (m, 2H), 2.19-2.27 (m, 1H), 2.46-2.54 (m, 1H), 2.76-2.87 (m, 1H), 3.30 (s, 3H, D1), 3.30 (s, 3H, D2), 3.76 (q, J=4.1 Hz, 1H), 4.61 (q, J=7.1 Hz, 2H, D1), 4.61 (q, J=7.1 Hz, 2H, D2), 5.23 (t, J=6.0 Hz, 1H), 5.53 (d, J=16.0 Hz, 1H), 5.58 (d, J=16.0 Hz, 1H), 6.75 (d, J=6.9 Hz, 2H), 6.88-6.95 (m, 7H), 6.98 (d, J=8.0 Hz, 2H), 7.17 (dt, J=2.0, 7.8 Hz, 1H), 7.23 (t, J=7.7 Hz, 6H), 7.26-7.34 (m, 4H), 7.40-7.48 (m, 2H), 7.54 (dd, J=1.1, 8.0 Hz, 1H), 7.76 (d, J=7.7 Hz, 1H), 7.86 (d, J=7.8 Hz, 1H); LC-MS: m/z 913.6 (M+H).

1. customthe reaction mixture was purified by column chromatography
2. washeluting with 10/90→70/30 ethyl acetate/hexanes