반응 #85479

반응 방정식

HCl

dimethyl malonate

sodium hydride

3,5-dichloro-3-(2-ethoxypyridin-3-yl)-6-fluoro-1,3-dihydroindol-2-one

→

title compound

수율 38.4%

Dimethyl 2-[5-chloro-3-(2-ethoxypyridin-3-yl)-6-fluoro-2-oxo-2,3-dihydro-1H-indol-3-yl]malonate

수율 38.4%

용매

dichloromethane

heptane ethyl acetate

dimethylformamide

반응 조건

후처리

1. 1
   workup.STIRRINGThe reaction mixture was then stirred for a further 15 minutes at room temperature
2. 2
   기타The phases were separated
3. 3
   추출the aqueous phase was extracted with dichloromethane (1×)
4. 4
   세척The combined organic phase was washed initially with water (1×)
5. 5
   건조with saturated sodium chloride solution (1×), dried over magnesium sulfate
6. 6
   여과filtered
7. 7
   기타the solvent was removed in vacuo
8. 8
   workup.DISSOLUTIONThe residue was again partly dissolved in a little dichloromethane, and pentane
9. 9
   workup.ADDITIONwas added
10. 10
    기타Several fractions of crystals were obtained

실험 절차

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.

출처