1-(5-Fluoro-2-methylphenyl)-3-trimethylsilyoxy-2-aza-1,3-butadiene → 6-chloro-4'-[5-chloro-2-(1-ethyl-1-methoxycarbonyl-propoxy)-phenyl]-2'-(5-fluoro-2-methyl-phenyl) spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

HRID 658914Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 658914
C(OC([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([Cl:17])[CH:15]=2)/[C:10](=[CH:18]/[C:19]2[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:20]=2[O:26][C:27]([C:32]([O:34][CH3:35])=[O:33])([CH2:30][CH3:31])[CH2:28][CH3:29])/[C:9]1=[O:36])=O)(C)(C)C.[F:37][C:38]1[CH:39]=[CH:40][C:41]([CH3:53])=[C:42]([CH:44]=[N:45][C:46]([O:48][Si](C)(C)C)=[CH2:47])[CH:43]=1>C1(C)C=CC=CC=1>[Cl:17][C:14]1[CH:15]=[C:16]2[NH:8][C:9](=[O:36])[C:10]3([CH:18]([C:19]4[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:20]=4[O:26][C:27]([CH2:28][CH3:29])([C:32]([O:34][CH3:35])=[O:33])[CH2:30][CH3:31])[CH2:47][C:46](=[O:48])[NH:45][CH:44]3[C:42]3[CH:43]=[C:38]([F:37])[CH:39]=[CH:40][C:41]=3[CH3:53])[C:11]2=[CH:12][CH:13]=1

Komponenten

4

Edukt 2

HCID 701785041-(5-Fluoro-2-methylphenyl)-3-trimethylsilyoxy-2-aza-1,3-butadieneHCID 86632089Z-3-[5-chloro-2-(1-ethyl-1-methoxycarbonyl-propoxy)-benzylidene]-6-chloro-2-oxo-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 722961936-chloro-4'-[5-chloro-2-(1-ethyl-1-methoxycarbonyl-propoxy)-phenyl]-2'-(5-fluoro-2-methyl-phenyl) spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dioneAusbeute 23,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

A mixture of E/Z-3-[5-chloro-2-(1-methoxycarbonyl-1-ethyl-propoxy)-benzylidene]-6-chloro-2-oxo-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester (7.6 g, 15 mmol) and 1-(5-fluoro-2-methyl-phenyl)-3-trimethylsilyoxy-2-aza-1,3-butadiene (60 mmol) prepared in Example 4 in toluene (60 mL) was heated at 60° C. for 3 h, and concentrated in vacuo. To the residue was added DCM (50 mL) and TFA (20 mL), and the resulting solution was stirred at room temperature for 3 h, then concentrated in vacuo, partitioned between ethyl acetate and diluted aqueous NaOH solution. The organic layer was washed with water, dried over anhydrous Na2SO4, and concentrated. The residue was purified by flash column chromatography to give the title compound as white solid (2.2 g).

Aufarbeitung

  1. concentrationconcentrated in vacuo
  2. additionTo the residue was added DCM (50 mL) and TFA (20 mL)
  3. concentrationconcentrated in vacuo
  4. custompartitioned between ethyl acetate and diluted aqueous NaOH solution
  5. washThe organic layer was washed with water
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by flash column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-0f42fde241724ea19dbb21eb5e23bf22
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08076482B2

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