1,4-Dioxane → 3-(4-fluoro-phenylmethyl)-1-methyl-1H-indole-5-carboxylic acid methyl ester

HRID 2195740

Reaktionsgleichung

Reaktionsgleichung von HRID 2195740
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH3:14])[CH:9]=[CH:8]2)=[O:4].[F:15][C:16]1[CH:23]=[CH:22][C:19]([CH2:20]Br)=[CH:18][CH:17]=1.O1CCOCC1>CCOCC>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH3:14])[CH:9]=[C:8]2[CH2:20][C:19]1[CH:22]=[CH:23][C:16]([F:15])=[CH:17][CH:18]=1)=[O:4]

Komponenten

5

Edukt 3

HCID 312751,4-DioxaneHCID 680214-Fluorobenzyl bromide2×HCID 10679201Methyl 1-methyl-1H-indole-5-carboxylate

Produkt 1

HCID 694495523-(4-fluoro-phenylmethyl)-1-methyl-1H-indole-5-carboxylic acid methyl esterAusbeute 22 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3283Diethyl EtherLösungsmittel

Versuchsvorschrift

A solution of 1-methyl-1H-indole-5-carboxylic acid methyl ester (0.17 g, 0.9 mmol), prepared using procedures as described in Example 1, Ag2O (0.22 g, 0.95 mmol), 4-fluoro-benzyl bromide (0.18 g, 0.95 mmol) and dioxane (4 mL) were heated to reflux for 16 hr, then more 4-fluoro-benzyl bromide (90 mg, 0.5 mmol) was added and the solution was heated at reflux an additional 4 hr. After cooling to room temperature, the reaction mixture was diluted with ether (60 mL), washed with aq. NH4Cl (50 mL) and then brine (50 mL). The organic layer was dried over MgSO4, filtered and concentrated. The remaining residue was subjected to flash chromatography (ethyl acetate/hexane, 1:3) to provide 3-(4-fluoro-phenylmethyl)-1-methyl-1H-indole-5-carboxylic acid methyl ester (58 mg, 22% yield).

Aufarbeitung

  1. temperaturewere heated
  2. temperatureto reflux for 16 hr
  3. temperaturethe solution was heated
  4. temperatureat reflux an additional 4 hr
  5. washwashed with aq. NH4Cl (50 mL)
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-191b2343760049c6955112d6e23c3b74
Quelldatensatz
uspto-grants-2012_12
Patentnummer
US08338416B2

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