反应详情

The reaction was also performed using the acylating agent dimethylcarbamoyl chloride. A solution of dimethylcarbamoyl chloride (12.9 mL, 0.14 mol) in dichloromethane (23 mL) was added drop-wise to a stirred solution of 3-bromo-2-chloropyridine 1-oxide (C27) (11.23 g, 53.9 mmol) and trimethylsilyl cyanide (17.5 mL, 0.14 mol) in dichloromethane (200 mL). The reaction mixture was heated under reflux for 3 days, then diluted with dichloromethane (450 mL) and washed with saturated aqueous sodium bicarbonate solution (2×200 mL), then with water (200 mL), dried over magnesium sulfate and concentrated in vacuo. Purification via silica gel chromatography (Gradient: 15% to 20% ethyl acetate in heptane) provided the title compound, contaminated with dimethylcarbamoyl cyanide (12.73 g, 100%) as an off-white solid. The impurity was reduced by repeatedly washing with aqueous sodium hydroxide solution (2 N) and a second chromatography on silica gel. Although the impurity could not be completely removed, the material was used in the next step without any detrimental effects. Yield: 7.83 g, 36.0 mmol, 67%. 1H NMR (400 MHz, CDCl3) δ 7.52 (d, J=7.8 Hz, 1H), 8.12 (d, J=7.8 Hz, 1H).

1. temperatureThe reaction mixture was heated
2. temperatureunder reflux for 3 days
3. washwashed with saturated aqueous sodium bicarbonate solution (2×200 mL)
4. dry with materialwith water (200 mL), dried over magnesium sulfate
5. concentrationconcentrated in vacuo
6. customPurification via silica gel chromatography (Gradient: 15% to 20% ethyl acetate in heptane)