Reaction #1144316

Reaction equation

NaHCO3

5-bromo-7-fluoro-1H-indazole

3,4-dihydro-2H-pyran

p-TsOH

→

5-bromo-7-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

Solvents

dichloromethane

Conditions

Workup

1. 1
   OtherThe organic layer was separated
2. 2
   Dryingdried over Na2SO4
3. 3
   Concentrationconcentrated in vacuo
4. 4
   OtherThe residue was purified by column chromatography on silica gel (0˜10% EtOAc in petroleum ether)

Procedure

To a mixture of 5-bromo-7-fluoro-1H-indazole (9.3 g, 43.26 mmol) and 3,4-dihydro-2H-pyran (4.36 g, 51.9 mmol) in dry dichloromethane (100 mL), was added p-TsOH (424 mg, 2.16 mmol) at room temperature. The resulting mixture was stirred overnight. Work-up: saturated aqueous NaHCO3 (30 mL) was slowly added to 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˜10% EtOAc in petroleum ether) to give 5-bromo-7-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole as a light yellow solid. (7.8 g). 1H NMR (300 MHz, CDCl3): δ 7.98 (s, 1H), 7.64 (s, 1H), 7.22 (dd, 1H), 5.84 (dd, 1H), 4.07-4.02 (m, 1H), 3.78-3.71 (m, 1H), 2.62-2.53 (m, 1H), 2.16-2.07 (m, 2H), 1.79-1.71 (m, 2H), 1.63-1.33 (m, 1H).

Source