Potassium methyl malonate → (E)-5-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]-3-oxopent-4-enoic acid methyl ester

HRID 352102ノート

反応式

HRID 352102 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]([CH:17]([CH3:19])[CH3:18])[C:9]=2/[CH:20]=[CH:21]/C(O)=O)=[CH:4][CH:3]=1.[Cl-].[Mg+2].[Cl-].[K+].[C:29]([O:35][CH3:36])(=[O:34])[CH2:30][C:31]([O-])=[O:32]>C1COCC1>[CH3:36][O:35][C:29](=[O:34])[CH2:30][C:31](=[O:32])/[CH:21]=[CH:20]/[C:9]1[N:10]([CH:17]([CH3:18])[CH3:19])[C:11]2[C:16]([C:8]=1[C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)=[CH:15][CH:14]=[CH:13][CH:12]=2

参加物

5

反応物 3

HCID 2724687Potassium methyl malonateHCID 5360315Magnesium ChlorideHCID 22715053(E)-3-[3-(4-Fluorophenyl)-1-isopropyl-1H-indol-2-yl]-acrylic Acid

生成物 1

HCID 11326444(E)-5-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]-3-oxopent-4-enoic acid methyl ester

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

0.8 g (2.46 mmol) of (E)-3-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]-acrylic acid in 4 ml of THF are introduced into a 50 ml three-necked round-bottomed flask equipped with a magnetic stirrer, thermometer, reflux condenser and nitrogen delivery line. 0.5 g (2.96 mmol) of 1,1-carbonyldiimidazole is then added in portions in the course of 5 min. and stirring is carried out at room temperature for 1 hour. 0.24 g (2.46 mmol) of magnesium chloride and 0.39 g (2.46 mmol) of monomethyl malonate potassium salt are then added and the suspension is stirred for 24 hours at 35° C. The reaction mixture is cooled and filtered and the residue is washed twice with 25 ml of THF. The filtrate is concentrated by evaporation, taken up in 30 ml of ethyl acetate, washed with 15 ml of 1N hydrochloric acid, three times with 20 ml of saturated sodium hydrogen carbonate solution and three times with saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated by evaporation. The residue is purified by means of flash chromatography (hexane/ethyl acetate=8:1). An orange resin is obtained which, according to NMR, is the product in a keto-enol equilibrium of approximately 3:1.

後処理

  1. customequipped with a magnetic stirrer
  2. temperaturethermometer, reflux condenser
  3. stirringthe suspension is stirred for 24 hours at 35° C
  4. temperatureThe reaction mixture is cooled
  5. filtrationfiltered
  6. washthe residue is washed twice with 25 ml of THF
  7. concentrationThe filtrate is concentrated by evaporation
  8. washwashed with 15 ml of 1N hydrochloric acid, three times with 20 ml of saturated sodium hydrogen carbonate solution and three times with saturated sodium chloride solution
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated by evaporation
  12. customThe residue is purified by means of flash chromatography (hexane/ethyl acetate=8:1)
  13. customAn orange resin is obtained which

出典と根拠

ORDレコード
ord-55a675aa50304516aefe0fef9f276f55
出典データセット
uspto-grants-2004_06
特許番号
US06743926B2

反応ノート

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