反应详情

温度

0 °C

A flask was charged with 5-bromo-7-(bromomethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (220 mg, 0.52 mmol), tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (160 mg, 0.55 mmol), and dimethylformamide (2.5 mL). The reaction was cooled to 0° C. and treated with sodium hydride (26.4 mg, 1.1 mmol) in several portions. After stirring for 15 min, the ice bath was removed and stirring continued for 15 min. The reaction was cooled to 0° C. and quenched by the cautious addition of saturated ammonium chloride. The reaction was poured into diethyl ether, washed with water (3×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (12%→25% EtOAc/Hex) gave 233 mg (71%) as a gum. 1H-NMR (CDCl3, 500 MHz) δ 7.87 (s, 1H), 7.78 (d, J=1.5 Hz, 1H), 7.27 (d, J=1.8 Hz, 1H), 7.19 (m, 5H), 5.32 (s, 2H), 4.65 (s, 2H), 3.67 (bs, 2H), 3.41 (s, 2H), 3.36 (t, J=8.2 Hz, 2H), 3.00 (m, 2H), 2.11 (m, 2H), 1.76 (m, 2H), 1.41 (s, 9H), 0.75 (t, J=8.2 Hz, 2H), −0.10 (s, 9H); 13C-NMR (CDCl3, 126 MHz) δ 155.0, 142.7, 137.1, 133.1, 131.4, 128.4, 127.8, 127.1, 126.4, 123.5, 122.8, 113.7, 79.4, 79.1, 78.8, 70.4, 66.0, 41.5, 40.2 (br), 32.1, 28.6, 17.8, −1.40.

1. customthe ice bath was removed
2. stirringstirring
3. waitcontinued for 15 min
4. temperatureThe reaction was cooled to 0° C.
5. customquenched by the cautious addition of saturated ammonium chloride
6. additionThe reaction was poured into diethyl ether
7. washwashed with water (3×)
8. dry with materialbrine, dried over magnesium sulfate
9. concentrationconcentrated
10. customColumn chromatography (12%→25% EtOAc/Hex) gave 233 mg (71%) as a gum