反应详情

To a mixture of 5-bromo-4-fluoro-1H-indazole (50 g, 0.23 mol) and 3,4-dihydro-2H-pyran (23 g, 0.28 mol) in dry dichloromethane (1000 mL) was added p-TsOH (2.2 g, 11.5 mmol) at room temperature. The resulting mixture was stirred overnight at that temperature. Upon completion, saturated aqueous NaHCO3 (100 mL) was added slowly into the reaction mixture. The organic layer was separated, dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (0˜2% EtOAc in petroleum ether) and then re-crystallized from petroleum ether to afford the title compound (55 g). 1H NMR (300 MHz, DMSO-d6): δ 8.28 (s, 1H), 7.58-7.66 (m, 2H), 5.89 (dd, 1H), 3.90-3.85 (m, 1H), 3.79-3.70 (m, 1H), 2.42-2.29 (m, 1H), 2.06-1.94 (m, 2H), 1.77-1.68 (m, 1H), 1.60-1.53 (m, 2H); LCMS: 299 (M+H)+.

1. customThe organic layer was separated
2. dry with materialdried over Na2SO4
3. concentrationconcentrated in vacuo
4. customThe residue was purified by column chromatography on silica gel (0˜2% EtOAc in petroleum ether)
5. customre-crystallized from petroleum ether