Water → Ethyl 3-(1'-methyl-2'-oxo-1',2,2',3-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-4'-yl)-3-oxopropanoate

HRID 1965334ノート

反応式

HRID 1965334 の反応式
[H-].[Na+].[C:3](=[O:10])([O:7][CH2:8][CH3:9])OCC.[C:11]([C:14]1[CH:22]=[CH:21][CH:20]=[C:19]2[C:15]=1[C:16]1([C:36]3[C:27](=[CH:28][C:29]4[O:34][CH2:33][CH2:32][O:31][C:30]=4[CH:35]=3)[O:26][CH2:25]1)[C:17](=[O:24])[N:18]2[CH3:23])(=[O:13])[CH3:12].O>O1CCCC1>[CH3:23][N:18]1[C:19]2[C:15](=[C:14]([C:11](=[O:13])[CH2:12][C:3]([O:7][CH2:8][CH3:9])=[O:10])[CH:22]=[CH:21][CH:20]=2)[C:16]2([C:36]3[C:27](=[CH:28][C:29]4[O:34][CH2:33][CH2:32][O:31][C:30]=4[CH:35]=3)[O:26][CH2:25]2)[C:17]1=[O:24]

参加物

6

反応物 4

HCID 962WaterHCID 7766Diethyl CarbonateHCID 24758Sodium hydrideHCID 685978014'-Acetyl-1'-methyl-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'H)-one

生成物 1

HCID 67357134Ethyl 3-(1'-methyl-2'-oxo-1',2,2',3-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-4'-yl)-3-oxopropanoate収率 39.6%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a suspension of sodium hydride (60% w/w dispersion in mineral oil, 0.11 g, 2.8 mmol) in anhydrous tetrahydrofuran (10 mL) at ambient temperature was added diethyl carbonate (0.26 mL, 2.1 mmol) and the mixture was heated at reflux for 5 min. 4′-Acetyl-1′-methyl-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.50 g, 1.4 mmol) was added in one portion and the reaction mixture was heated at reflux for 16 h, allowed to cool to ambient temperature and poured into water (75 mL). The mixture was extracted with dichloromethane (3×50 mL). The combined organic extracts were washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography and eluted with a 0% to 10% gradient of ethyl acetate in dichloromethane, followed by recrystallization from dichloromethane/diethyl ether to afford ethyl 3-(1′-methyl-2′-oxo-1′,2,2′,3-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-4′-yl)-3-oxopropanoate (0.235 g, 39%) as a pale yellow solid: 1H NMR (300 MHz, CDCl3) δ 7.50-7.43 (m, 2H), 7.14-7.09 (m, 1H), 6.51 (s, 1H), 6.02 (s, 1H), 4.97-4.78 (m, 2H), 4.20-4.03 (m, 6H), 3.89 (d, J=15.6 Hz, 1H), 3.65 (d, J=15.6 Hz, 1H), 3.29 (s, 3H), 1.16 (t, J=7.1 Hz, 3H); MS (ES+) m/z 445.8 (M+23).

後処理

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 5 min
  3. temperaturethe reaction mixture was heated
  4. temperatureat reflux for 16 h
  5. extractionThe mixture was extracted with dichloromethane (3×50 mL)
  6. washThe combined organic extracts were washed with brine (50 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by column chromatography
  11. washeluted with a 0% to 10% gradient of ethyl acetate in dichloromethane
  12. customfollowed by recrystallization from dichloromethane/diethyl ether

出典と根拠

ORDレコード
ord-6ca82f0b4910456f94e28cfd56676c80
出典データセット
uspto-grants-2013_04
特許番号
US08415370B2

反応ノート

読み込み中…