反应详情

温度

0 °C

To a solution of (±)-1-(5-fluoro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole-7-yl)ethyl 2,2,2-trichloroacetimidate (1.121 g, 2.465 mmol) and tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate (0.839 g, 2.71 mmol) in dichloromethane (6 mL) at 0° C. was added cyclohexane (5.61 mL) and tetrafluoroboric acid diethyl ether complex (0.017 mL, 0.123 mmol). The reaction was stirred at 0° C. for 10 min. The reaction was treated with an additional portion of tetrafluoroboric acid diethyl ether complex (9 μL, 0.065 mmol) and stirred at 0° C. for 30 min. The reaction was quenched by addition of saturated sodium bicarbonate, diluted with diethyl ether, and poured into water. The ethereal was washed with water (2×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (15%→22% EtOAc/Hex) gave 922 mg (62.2%) as an amorphous foam solid. 1H-NMR (CDCl3, 300 MHz) δ 7.98 (s, 1H), 7.26-7.32 (m, 2H), 6.97-7.08 (m, 3H), 6.64-6.68(m, 1H), 5.62 (s, 2H), 4.92 (q, J=6.0 Hz, 1H), 3.65-3.75 (m, 2H), 3.58 (m, 2H), 3.35 (m, 2H), 2.9-3.1 (m, 2H), 1.8-2.2 (m, 4H), 1.39-1.42(m, 12H), 0.88(m, 2H), −0.07 (s, 9H); Mass spec.: 602.54 (MH)+.

1. additionThe reaction was treated with an additional portion of tetrafluoroboric acid diethyl ether complex (9 μL, 0.065 mmol)
2. stirringstirred at 0° C. for 30 min
3. customThe reaction was quenched by addition of saturated sodium bicarbonate
4. additiondiluted with diethyl ether
5. additionpoured into water
6. washThe ethereal was washed with water (2×)
7. dry with materialbrine, dried over magnesium sulfate
8. concentrationconcentrated
9. customColumn chromatography (15%→22% EtOAc/Hex) gave 922 mg (62.2%) as an amorphous foam solid