Reaction Steps
To a solution of tert-butyl 4-((1-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)-2-hydroxyethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (50 mg, 0.079 mmol) in acetonitrile (0.1 mL) at room temperature was added diisopropylethylamine (0.062 mL, 0.355 mmol), diisopropylethylamine trihydrofluoride (22.4 mg, 0.118 mmol), and perfluoro-1-butanesulfonyl fluoride (0.028 mL, 0.16 mmol). The reaction was stirred at room temperature overnight. The reaction was poured into saturated sodium bicarbonate, and diluted with diethyl ether. The ethereal was washed with water, then brine, dried over magnesium sulfate, and concentrated. Column chromatography (15%→20% ethyl acetate/n-hexane) gave 40 mg (80%) as a colorless film. 1H-NMR (CDCl3, 500 MHz) δ 8.01 (s, 1H), 7.54 (d, J=1.8 Hz, 1H), 7.33 (dd, J=9.2, 5.5 Hz, 2H), 7.03 (dd, J=8.9, 8.5 Hz, 2H), 6.73 (bs, 1H), 5.66 (d, J=10.7 Hz, 1H), 5.63 (d, J=10.7 Hz, 1H), 5.16 (m, 1H), 4.62 (ddd, J=46.7, 9.5, 2.4 Hz, 1H), 4.42 (ddd, J=48.2, 9.8, 7.3 Hz, 1H), 3.75 (bs, 2H), 3.60 (m, 2H), 3.52 (d, J=9.2 Hz, 1H), 3.45 (d, J=9.2 Hz, 1H), 3.10 (bs, 1H), 3.03 (m, 1H), 2.27 (m, 1H), 2.07 (m, 1H), 1.99 (m, 1H), 1.87 (m, 1H), 1.44 (s, 9H), 0.92 (m, 2H), −0.05 (s, 9H); 13C NMR (126 MHz, CDCl3) δ ppm 161.5 (d, J=246 Hz), 155.1, 145.4, 138.5, 128.9 (d, J=7.7 Hz), 128.2, 128.11, 128.07, 124.9, 122.7, 122.6, 118.9, 115.3 (d, J=21 Hz), 85.9, 84.4, 81.9, 79.5, 78.8, 77.3, 77.1, 67.8, 41.5, 40.5, 39.7, 32.2, 31.8, 28.6, 17.9, −1.4. Mass spec.: 636.43 (MH)+.
