Tributyltin Chloride → 5-(difluoromethoxy)-3-(tributylstannyl)-1H-indazole

Temperature

-25 °C

In a flask, 5-(difluoromethoxy)-3-iodo-1H-indazole (1.2 g, 2.93 mmol) was dissolved in THF (30 mL). The solution was cooled to −25° C. Isopropylmagnesium chloride (8.8 mL, 8.8 mmol, 1M in THF) was added drop-wise at −25° C. The reaction mixture was stirred at −25° C. for 20 min. Then chlorotributyltin (1.6 mL, 5.86 mmol) was added slowly. The reaction mixture was allowed to warm to room temperature and stirred for 1.5 h. The reaction mixture was quenched with saturated NH4Cl solution and then extracted with EtOAc (3×20 mL), organics were washed with water (10 mL), brine (2×10 mL) and dried over Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel eluting with petroleum ether/EtOAc (8:1) to give 5-(difluoromethoxy)-3-(tributylstannyl)-1H-indazole (1.1 g, 79%) as an oil. 1H NMR (300 MHz, CDCl3): δ 7.52-7.46 (m, 2H), 7.19 (d, 1H, J=7.9 Hz), 6.51 (t, 1H, J=88.6 Hz), 1.68-1.57 (m, 6H), 1.45-1.14 (m, 12H), 0.93-0.84 (m, 9H).

1. temperatureto warm to room temperature
2. stirringstirred for 1.5 h
3. customThe reaction mixture was quenched with saturated NH4Cl solution
4. extractionextracted with EtOAc (3×20 mL)
5. washorganics were washed with water (10 mL), brine (2×10 mL)
6. dry with materialdried over Na2SO4
7. concentrationconcentrated
8. customThe residue was purified by column chromatography on silica gel eluting with petroleum ether/EtOAc (8:1)

ORD record

ord-70b4b70caa984c0288cb7e98cfc37b9f

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658646B2