Water → 4-Nitro-2-{[2-(trimethylsilyl)ethoxy]methyl}-2H-indazole

Participants

Reaction Steps

To a solution of 4nitroindazole (2.55 g, 15.6 mmol) in anhydrous dimethylformamide (20 ml) at room temperature was added sodium hydride (902 mg, 37.6 mmol, 2.4 eq, 60% dispersion in oil) portionwise. This was allowed to stir at room temperature for 10 minutes. 2-(Chloromethoxy)ethyl-trimethylsilane (3.3 ml, 18.8 mmol, 1.2 eq) was added and the reaction stirred at room temperature for a further 90 minutes. Water (30 ml) was added and the reaction extracted into diethyl ether (2×50 ml). The combined organic layers were washed with brine (2×50 ml), the layers separated and the organic layer dried over MgSO4, filtered and evaporated. The resulting oil was purified by column chromatography on silica eluting with 20% ethyl acetate in isohexane, to give 4-nitro-1-{[2-trimethylsilylethoxy]methyl}-1H-indazole (1.74 g, 38%) as the less polar product and 4-nitro-2-{[2-trimethylsilylethoxy]methyl}-2H-indazole (1.93 g, 42%) as the more polar product. 1H NMR—1-Substituted isomer—(360 MHz, CDCl3) δ 0.00 (9H, s), 0.94 (2H, t, J 8.4), 3.63 (2H, t, J 8.2), 5.89 (2H, s), 7.62 (1H, t, J 8.0), 8.03 (1H, d, J 8.3), 8.26 (1H, d, J 7.7), 8.71 (1H, s).

Provenance & Evidence