(3-Chloro-2-fluorophenyl)hydrazine → 4-(6-chloro-3-ethyl-7-fluoro-1H-indol-2-yl)-2-hydroxy-benzoic acid methyl ester

HRID 1160795Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1160795
[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[CH:8][C:7]([C:10](=O)[CH2:11][CH2:12][CH3:13])=[CH:6][C:5]=1[OH:15].[Cl:17][C:18]1[C:19]([F:26])=[C:20]([NH:24]N)[CH:21]=[CH:22][CH:23]=1>C(O)(=O)C.[Cl-].[Zn+2].[Cl-]>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[NH:24][C:20]3[C:21]([C:11]=2[CH2:12][CH3:13])=[CH:22][CH:23]=[C:18]([Cl:17])[C:19]=3[F:26])=[CH:6][C:5]=1[OH:15]

Komponenten

5

Edukt 2

HCID 2778381(3-Chloro-2-fluorophenyl)hydrazineHCID 595180214-Butyryl-2-hydroxy-benzoic acid methyl ester

Produkt 1

HCID 595180204-(6-chloro-3-ethyl-7-fluoro-1H-indol-2-yl)-2-hydroxy-benzoic acid methyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3007855ZincchlorideKatalysatorHCID 176Acetic AcidLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A mixture of 4-butyryl-2-hydroxy-benzoic acid methyl ester (60 mg, 0.27 mmol), (3-chloro-2-fluoro-phenyl)-hydrazine (Apollo Scientific, Ltd., 54 mg, 0.27 mmol), and zinc chloride (110 mg, 0.8 mmol) in acetic acid (2 mL) is purged with nitrogen for 5 minutes and then heated in a sealed tube at 120° C. for 2 hours. The mixture is cooled to room temperature and diluted with ethyl acetate. The resulting mixture is sequentially washed with saturated aqueous Na2CO3 and saturated aqueous NaCl, and finally dried over sodium sulfate. After concentration, the crude product is purified via silica gel flash column chromatography (10% ethyl acetate in hexanes) to afford 4-(6-chloro-3-ethyl-7-fluoro-1H-indol-2-yl)-2-hydroxy-benzoic acid methyl ester as a light yellow solid: ESMS m/z 348.1 (M+H+).

Aufarbeitung

  1. customis purged with nitrogen for 5 minutes
  2. temperatureThe mixture is cooled to room temperature
  3. additiondiluted with ethyl acetate
  4. washThe resulting mixture is sequentially washed with saturated aqueous Na2CO3 and saturated aqueous NaCl
  5. dry with materialfinally dried over sodium sulfate
  6. concentrationAfter concentration
  7. customthe crude product is purified via silica gel flash column chromatography (10% ethyl acetate in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-c96e38f34770433eaef37cda5194a561
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07816542B2

Notizen zur Reaktion

Wird geladen…