반응 #582614
ord-63a1670f604343d7a33e9eed326b5d3c
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반응 조건
후처리
- 1workup.ADDITIONwas added, portionwise over 0.2 h
- 2기타Internal temperature was kept ≦30° C. by external ice bath
- 3온도cooling
- 4추출was extracted with toluene (4×50 mL)
- 5세척The combined extracts were washed with water (4×50 mL) and brine (50 mL)
- 6건조dried (Na2SO4)
- 7기타evaporated in vacuo
- 8기타to give an oil
- 9세척Chromatography of the residue on silica with 5-50% ether in hexane gradient elution
실험 절차
To a mixture of 4-methoxyindole (1.26 g, 8.57 mmol), powdered potassium hydroxide (10.05 g, 0.179 mol) and dry dimethylformamide (20 mL) at 15° C. under argon was added, portionwise over 0.2 h, hydroxylamine-O-sulfonic acid. Internal temperature was kept ≦30° C. by external ice bath cooling. The mixture was stirred at 20° C. for 4 h, then was extracted with toluene (4×50 mL). The combined extracts were washed with water (4×50 mL) and brine (50 mL), then dried (Na2SO4) and evaporated in vacuo to give an oil. Chromatography of the residue on silica with 5-50% ether in hexane gradient elution gave 1-amino-4-methoxyindole (0.79 g, 56%). A mixture of 1-amino-4-methoxyindole (0.78 g, 4.8 mmol), nitrobenzene (3.4 g, 27.8 mmol), and methanolic HCl (3% w/w, 180 mL) was heated at reflux for 76 h, then cooled and partitioned between 10% aqueous NaOH (50 mL) and dichloromethane (3×30 mL). The combined organic extracts were dried (Na2SO4) and evaporated in vacuo to give an oil which was purified by chromatography on silica with 5-100% ether in hexane gradient elution. The resulting 5-methoxycinnoline (0.56 g, 3.5 mmol) was mixed with 48% aqueous HBr (35 mL) and the resulting solution heated at reflux for 18 h. The mixture was cooled, then evaporated in vacuo, and the residue dissolved in water (10 mL). Aqueous ammonia (d=0.880) was added until pH 6 was obtained, and the resulting mixture cooled to 0° C. The precipitated solid was collected by filtration and purified by charcoal-methanol treatment to give the title compound (0.37 g, 53%) as a yellow solid.