4-Fluorophenol → 4-methyl-1-(2-(4-fluorophenoxycarbonyl)-1H-indol-4-yl)piperazine

HRID 1383329Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1383329
C(C1NC=CN=1)(C1NC=CN=1)=O.[CH3:13][N:14]1[CH2:19][CH2:18][N:17]([C:20]2[CH:28]=[CH:27][CH:26]=[C:25]3[C:21]=2[CH:22]=[C:23]([C:29]([OH:31])=[O:30])[NH:24]3)[CH2:16][CH2:15]1.[F:32][C:33]1[CH:38]=[CH:37][C:36](O)=[CH:35][CH:34]=1.[H-].[Na+]>O1CCCC1.C(OCC)(=O)C>[CH3:13][N:14]1[CH2:19][CH2:18][N:17]([C:20]2[CH:28]=[CH:27][CH:26]=[C:25]3[C:21]=2[CH:22]=[C:23]([C:29]([O:31][C:36]2[CH:37]=[CH:38][C:33]([F:32])=[CH:34][CH:35]=2)=[O:30])[NH:24]3)[CH2:16][CH2:15]1

Komponenten

7

Edukt 4

HCID 97324-FluorophenolHCID 24758Sodium hydrideHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 211875904-(4-Methylpiperazin-1yl)indole-2-carboxylic acid

Produkt 1

HCID 211875494-methyl-1-(2-(4-fluorophenoxycarbonyl)-1H-indol-4-yl)piperazineAusbeute 25 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A solution of carbonyl diimidazole (0.95 g, 5.86 mmol, 2.1 equivalents) and 4-(4-Methylpiperazin-1 yl)indole-2-carboxylic acid (0.710 g, 2.74 mmol) in anhydrous tetrahydrofuran (5 mL) was heated at 50° C. under nitrogen for 5 hours. The reaction was cooled to room temperature, and a preformed solution of 4-fluorophenol (2.90 g, 25.9 mmol, 9.4 equivalents) and sodium hydride (60% in oil, 1.17 g, 29.2 mmol, 10,7 equivalents) in anhydrous tetrahydrofuran (15 mL) was added rapidly. The resulting reaction solution was stirred at room temperature under nitrogen for 12 hours. Ethyl acetate (50 mL) was added to the reaction solution, and the resulting solution was extracted with a saturated solution of sodium hydrogen carbonate (2×25 mL). The organic layer was dried (magnesium sulfate), and evaporated under reduced pressure. The residue was chromatographed using silica gel (approximately 100 g) and elution with 20% methanol in ethyl acetate to afford crude 4-methyl-1-(2-(4-fluorophenoxycarbonyl)-1H-indol-4-yl)piperazine (0.225 g, 0.68 mmol crude, 25% crude).

Aufarbeitung

  1. customThe resulting reaction solution
  2. extractionthe resulting solution was extracted with a saturated solution of sodium hydrogen carbonate (2×25 mL)
  3. dry with materialThe organic layer was dried (magnesium sulfate)
  4. customevaporated under reduced pressure
  5. customThe residue was chromatographed
  6. washsilica gel (approximately 100 g) and elution with 20% methanol in ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-227fd383f65e4baca48e62e2f937def3
Quelldatensatz
uspto-grants-2001_07
Patentnummer
US06255306B1

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