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N-methyl-2-pyrrolidone → 5-Cyano-3,4-difluoro-2-(2-fluorophenylamino)-benzoic acid methyl ester

HRID 500576
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 500576
[CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[C:8](Br)[C:7]([F:11])=[C:6]([F:12])[C:5]=1[NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[F:20].[CH3:22][N:23]1C(=O)CCC1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[C-]#N.[C-]#N.[Zn+2]>[CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[C:8]([C:22]#[N:23])[C:7]([F:11])=[C:6]([F:12])[C:5]=1[NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[F:20]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

6

Edukt 2

HCID 13387N-methyl-2-pyrrolidoneHCID 59519391Methyl 5-bromo-2-(2-fluorophenylamino)-3,4-difluorobenzoate

Produkt 1

HCID 865986425-Cyano-3,4-difluoro-2-(2-fluorophenylamino)-benzoic acid methyl ester

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11186Zinc cyanide (Zn(CN)2)KatalysatorHCID 635956
Ferrocene-1,1'-bis-(diphenylphosphine)
Katalysator
HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysator

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A mixture of 5-bromo-3,4-difluoro-2-(2-fluorophenylamino)-benzoic acid methyl ester (1.00 equiv.), dppf (0.02 equiv.), Pd2dba3 (0.01 equiv.), and Zn(CN)2 (0.60 equiv.) in NMP is stirred at 120° C. in a sealed tube. After stirring for 20 hours, the reaction mixture is cooled to room temperature and quenched with a 4:1:4 (volume) mixture solution of saturated aqueous NH4Cl-conc NH4O-water. The mixture is extracted with EtOAc. The organic layer is washed with saturated aqueous NH4Cl/concentrated NH4OH/water, and brine. The organic layer is dried over MgSO4, filtered, and concentrated under reduced pressure to give the crude material that is purified by flash column chromatography to afford the desired product.

Aufarbeitung

  1. stirringAfter stirring for 20 hours
  2. temperaturethe reaction mixture is cooled to room temperature
  3. customquenched with a 4:1:4 (volume) mixture solution of saturated aqueous NH4Cl-conc NH4O-water
  4. extractionThe mixture is extracted with EtOAc
  5. washThe organic layer is washed with saturated aqueous NH4Cl/concentrated NH4OH/water, and brine
  6. dry with materialThe organic layer is dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give the crude material that
  10. customis purified by flash column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-a7036860263343c48869817e57257f9a
Quelldatensatz
uspto-grants-2010_08
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07772234B2

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