反应详情

温度

0 °C

To a solution of tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (0.669 g, 2.3 mmol) and 7-(bromomethyl)-5-(trifluoromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (0.94 g, 2.3 mmol) in dimethylformamide (7 mL) at 0° C. was added sodium hydride (60% in mineral oil, 0.119 g, 3.0 mmol). The resulting solution was stirred at 0° C. for 30 min. The reaction was quenched by the cautious addition of saturated ammonium chloride and diluted with diethyl ether. The ethereal was washed with water (2×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (12% EtOAc/Hex) gave 1.13 g (79%) as an oil. 1H-NMR (CDCl3, 500 MHz) δ 8.03 (s, 1H), 7.98 (s, 1H), 7.41 (d, J=0.9 Hz, 1H), 7.10-7.28 (m, 5H), 5.37 (s, 2H), 4.73 (s, 2H), 3.69 (bs, 2H), 3.45 (s, 2H), 3.39 (m, 2H), 3.01 (m, 2H), 2.13 (m, 2H), 1.77 (m, 2H), 1.41 (s, 9H), 0.77 (m, 2H), −0.11 (s, 9H); 13C-NMR (CDCl3, 126 MHz) δ 155.0 142.7, 139.3, 134.7, 128.4, 127.1, 126.4, 125.6, 124.8, 124.6 (q, J=273 Hz), 123.5 (q, J=32 Hz), 122.1, 119.2, 79.4, 79.2, 79.0, 70.6, 66.1, 41.5, 40.3 (br), 32.2, 28.5, 17.8, −1.4. Mass spec.: 620.15 (MH)+.

1. customThe reaction was quenched by the cautious addition of saturated ammonium chloride
2. additiondiluted with diethyl ether
3. washThe ethereal was washed with water (2×)
4. dry with materialbrine, dried over magnesium sulfate
5. concentrationconcentrated
6. customColumn chromatography (12% EtOAc/Hex) gave 1.13 g (79%) as an oil