反应详情

7.26 ml (63.5 mmol) of dimethyl malonate were slowly added dropwise to a suspension, cooled to 10° C., of 2.311 g (57.8 mmol, 60% w/w) of sodium hydride in 150 ml of dimethylformamide. The reaction mixture was then stirred at room temperature for 30 minutes and subsequently 6.57 g (19.26 mmol) of 3,5-dichloro-3-(2-ethoxypyridin-3-yl)-6-fluoro-1,3-dihydroindol-2-one (prepared using 5-chloro-3-(2-ethoxypyridin-3-yl)-6-fluoro-3-hydroxy-1,3-dihydroindol-2-one in analogy to example 1.1) was added in portions undiluted. The reaction mixture was then stirred for a further 15 minutes at room temperature. The progress of the reaction was monitored by thin-layer chromatography (silica gel, heptane/ethyl acetate 1:1). The mixture was worked up by stirring into cold 1N HCl and adding dichloromethane. The phases were separated, and the aqueous phase was extracted with dichloromethane (1×). The combined organic phase was washed initially 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 fractions of crystals were obtained. In total, 3.23 g of the title compound were obtained as a white solid and 1.62 g as a beige-colored solid.

1. stirringThe reaction mixture was then stirred for a further 15 minutes at room temperature
2. customThe phases were separated
3. extractionthe aqueous phase was extracted with dichloromethane (1×)
4. washThe combined organic phase was washed initially 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 fractions of crystals were obtained