反应详情

5.68 ml (49.75 mmol) of dimethyl malonate were slowly added dropwise to a suspension, cooled to 10° C., of 1.808 g (45.23 mmol, 60% w/w) of sodium hydride in 100 ml of dimethylformamide. The reaction mixture was then stirred at room temperature for 30 minutes and subsequently 4.73 g (15.08 mmol) of 3-chloro-3-(2-ethoxypyridin-3-yl)-2-oxoindoline-5-carbonitrile from example 1.3 were added in portions undiluted. The reaction solution became dark red in color and was stirred at room temperature for a further 15 minutes. The progress of the reaction was checked by thin-layer chromatography (silica gel, heptane/ethyl acetate 1:1). The mixture was worked up by stirring into cold 1 N HCl and adding dichloromethane. The phases were separated, and the aqueous phase was extracted with dichloromethane (1×). The combined organic phase was washed firstly with water (1×) and then with saturated sodium chloride solution (1×), dried over magnesium sulfate and filtered, and the solvent was removed in vacuo. The residue was again partly dissolved in a little dichloromethane, and pentane was added. Several crystalline fractions were obtained. A total of 6.48 g (15.83 mmol, 100%) of the title compound was obtained as a yellow solid which was only slightly impure.

1. stirringwas stirred at room temperature for a further 15 minutes
2. customThe phases were separated
3. extractionthe aqueous phase was extracted with dichloromethane (1×)
4. washThe combined organic phase was washed firstly with water (1×)
5. dry with materialwith saturated sodium chloride solution (1×), dried over magnesium sulfate
6. filtrationfiltered
7. customthe solvent was removed in vacuo
8. dissolutionThe residue was again partly dissolved in a little dichloromethane, and pentane
9. additionwas added
10. customSeveral crystalline fractions were obtained