Water → 7-bromo-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-Indazole

HRID 246663Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][N:8]=[CH:7]2.[H-].[Na+].Cl[CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19].O>O1CCCC1>[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[N:8]=[CH:7]2

Participants

Conditions

Temperature: 20 °C

Procedure

To a solution of 7-bromo-1H-indazole (1 g, 5.1 mmol) in dry tetrahydrofuran (20 mL) was added NaH (305 mg, 60%, 7.65 mmol) at −20° C. under N2 atmosphere. After 20 minutes, (2-(chloromethoxy)ethyl)trimethylsilane (1 g, 6.1 mmol) was added and the mixture was warmed to 20° C. and stirred for 1 hour. Water (2 mL) was added and product extracted with dichloromethane (100 mL), organic phase washed with water (2×10 mL) and brine (2×10 mL) then dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography (silica gel, 200-300 mesh, eluting with ethyl acetate:petroleum ether=1:20) to afford 7-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (1.27 g, 77%) as a yellow oil. 1H NMR (300 MHz, CDCl3): δ 8.03 (s, 1H), 7.69 (d, 1H, J=8.7 Hz), 7.60 (d, 1H, J=8.1 Hz), 7.06-7.01 (m, 1H), 6.08 (s, 2H), 3.60 (t, 2H, J=7.8 Hz), 0.90 (d, 2H, J=8.1 Hz), 0.01 (s, 9H).

Workup

extractionproduct extracted with dichloromethane (100 mL), organic phase
washwashed with water (2×10 mL) and brine (2×10 mL)
dry with materialthen dried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified by column chromatography (silica gel, 200-300 mesh, eluting with ethyl acetate:petroleum ether=1:20)

Sources & evidence

ORD record: ord-7f1585637fb7480aa2f7d74f7074cfe3
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658646B2

Reaction notes

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