Hydrochloric Acid → Dimethyl [5-cyano-3-(2-ethoxypyridin-3-yl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-malonate

HRID 2368451ノート

反応式

HRID 2368451 の反応式
[C:1]([O:8][CH3:9])(=[O:7])[CH2:2][C:3]([O:5][CH3:6])=[O:4].[H-].[Na+].Cl[C:13]1([C:25]2[C:26]([O:31][CH2:32][CH3:33])=[N:27][CH:28]=[CH:29][CH:30]=2)[C:21]2[C:16](=[CH:17][CH:18]=[C:19]([C:22]#[N:23])[CH:20]=2)[NH:15][C:14]1=[O:24].Cl>CN(C)C=O.ClCCl.CCCCCCC.C(OCC)(=O)C>[CH3:6][O:5][C:3](=[O:4])[CH:2]([C:13]1([C:25]2[C:26]([O:31][CH2:32][CH3:33])=[N:27][CH:28]=[CH:29][CH:30]=2)[C:21]2[C:16](=[CH:17][CH:18]=[C:19]([C:22]#[N:23])[CH:20]=2)[NH:15][C:14]1=[O:24])[C:1]([O:8][CH3:9])=[O:7]

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 7943Dimethyl malonateHCID 24758Sodium hydrideHCID 670485043-Chloro-3-(2-ethoxypyridin-3-yl)-2-oxoindoline-5-carbonitrile

生成物 1

HCID 67048639Dimethyl [5-cyano-3-(2-ethoxypyridin-3-yl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-malonate収率 105%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 21899848Ethylacetate heptane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-c09718c981074f668ff30eca9021ab7c
出典データセット
uspto-grants-2014_04
特許番号
US08703775B2

反応ノート

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