Oxazole → 1-butyl-4-(1,3-oxazol-2-yl)-1H-indole-6-carboxylic acid

HRID 348969

Reaktionsgleichung

Reaktionsgleichung von HRID 348969
[O:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[CH2:6]([N:10]1[C:18]2[C:13](=[C:14](I)[CH:15]=[C:16]([C:19]([O:21]C)=[O:20])[CH:17]=2)[CH:12]=[CH:11]1)[CH2:7][CH2:8][CH3:9]>C1COCC1.[Cl-].[Zn+2].[Cl-]>[CH2:6]([N:10]1[C:18]2[C:13](=[C:14]([C:2]3[O:1][CH:5]=[CH:4][N:3]=3)[CH:15]=[C:16]([C:19]([OH:21])=[O:20])[CH:17]=2)[CH:12]=[CH:11]1)[CH2:7][CH2:8][CH3:9]

Komponenten

5

Edukt 2

HCID 9255OxazoleHCID 21086136Methyl 1-butyl-4-iodo-1H-indole-6-carboxylate

Produkt 1

HCID 210851691-butyl-4-(1,3-oxazol-2-yl)-1H-indole-6-carboxylic acidAusbeute 70,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3007855ZincchlorideKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

To a −72° C. solution of oxazole (0.069 g) in dry THF (20 mL) was added dropwise 1.6 M N-butyl lithium (0.68 mL). The mixture was stirred at −72° C. for 30 minutes at which time 1.0 M zinc chloride (3.3 mL) was added. The mixture was allowed to warm to 0° C. at which time methyl 1-butyl-4-iodo-1H-indole-6-carboxylate (0.37 g) and tetrakis triphenylphosphine palladium (0) (0.07 g) were added and the mixture heated to 85° C. The mixture was heated at 85° C. for 20 h then cooled to room temperature and partitioned between water and ethyl acetate. The layers were separated and the organic layer washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Column chromatography was performed on silica gel (100 mL) using 20% ethyl acetate in hexanes as eluent. The residue was dissolved in methanol (10 mL) and 1N NaOH (3 mL) and heated at 60° C. for 2 h. The mixture was acidified to pH 4 with 1N HCl and extracted with ethyl acetate. The ethyl acetate extracts were dried over anhydrous sodium sulfate and concentrated to dryness under reduced pressure to give 0.2 g of the title compound: MS (ESI+) for C16H16N2O3 m/z 283.16 (M+H)+.

Aufarbeitung

  1. additionwas added
  2. additionwere added
  3. temperatureThe mixture was heated at 85° C. for 20 h
  4. temperaturethen cooled to room temperature
  5. custompartitioned between water and ethyl acetate
  6. customThe layers were separated
  7. washthe organic layer washed with water
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. dissolutionThe residue was dissolved in methanol (10 mL)
  11. temperature1N NaOH (3 mL) and heated at 60° C. for 2 h
  12. extractionextracted with ethyl acetate
  13. dry with materialThe ethyl acetate extracts were dried over anhydrous sodium sulfate
  14. concentrationconcentrated to dryness under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-31281ac5b62a447f899f985add8c2009
Quelldatensatz
uspto-grants-2007_02
Patentnummer
US07176242B2

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