反应详情

A sample of N1-benzyl-6-vinyl-1H-indazole (crude material, ˜24 mmol) was stirred in a mixture of tBuOH (25 mL), water (25 mL) and citric acid (10.1 g, 48.0 mmol). K2OsO4.2H2O (44 mg, 0.12 mmol, 0.5 mol %) and N-methylmorpholine-N-oxide (3.1 g, 26.4 mmol) were added, and the resulting oily, biphasic mixture stirred overnight at rt. 1H NMR of a sample showed approx. 40% conversion, and so the mixture was warmed to 50° C. (giving a single phase) for 7 h. Ethanol (50 mL) was added, and the mixture again left to stir overnight. Precipitated OsO2 was removed by filtration through celite (washing with ethanol and ethyl acetate), and the filtrate was concentrated on a rotary evaporator. The residue was taken up in 1.0 M aq. HCl and EtOAc; the layers were separated and the aqueous phase extracted with further EtOAc. The combined organic portions were washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was passed through a short silica plug, eluting with EtOAc, and concentrated to afford the title compound (6.26 g, 92% over two steps) as a reddish gum. 1H NMR (400 MHz, CDCl3) δ 7.96 (s, 1H), 7.65 (d, J=8.4 Hz, 1H), 7.38 (s, 1H), 7.27-7.18 (m, 3H), 7.16-7.09 (m, 2H), 7.04 (d, J=8.4 Hz, 1H), 5.50 (s, 2H), 4.86 (d, J=7.6 Hz, 1H), 3.78-3.68 (m, 1H), 3.60 (m, 1H), 3.46 (s, 1H), 2.84 (s, 1H). MS (ES+): 269 ([M+H]+), calcd for [C16H16N2O2+H]+ 269.1.

1. temperatureso the mixture was warmed to 50° C. (
2. customgiving a single phase) for 7 h
3. waitthe mixture again left
4. stirringto stir overnight
5. customPrecipitated OsO2 was removed by filtration through celite (washing with ethanol and ethyl acetate)
6. concentrationthe filtrate was concentrated on a rotary evaporator
7. customthe layers were separated
8. extractionthe aqueous phase extracted with further EtOAc
9. washThe combined organic portions were washed with brine
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated
13. washeluting with EtOAc
14. concentrationconcentrated