Morpholine → HCID 86699759, Verbindung

HRID 515194Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 515194
C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[C:48]1[CH:64]=[C:63]([O:65][CH3:66])[C:51]([C:52]([NH:54][CH2:55][C:56]2[CH:61]=[CH:60][C:59]([Cl:62])=[CH:58][CH:57]=2)=[O:53])=[C:50]([F:67])[CH:49]=1.[NH:68]1[CH2:73][CH2:72][O:71][CH2:70][CH2:69]1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.O.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]>[Cl:62][C:59]1[CH:60]=[CH:61][C:56]([CH2:55][NH:54][C:52](=[O:53])[C:51]2[C:63]([O:65][CH3:66])=[CH:64][C:48]([N:68]3[CH2:73][CH2:72][O:71][CH2:70][CH2:69]3)=[CH:49][C:50]=2[F:67])=[CH:57][CH:58]=1

Komponenten

8

Edukt 4

HCID 8083MorpholineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 86699758HCID 86699758, Verbindung

Produkt 1

HCID 86699759HCID 86699759, VerbindungAusbeute 42,6 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (468 mg, 0.75 mmol) is added to a stirred solution of 4-bromo-N-[(4-chlorophenyl)-methyl]-2-fluoro-6-methoxy-benzamide (2.8 g, 7.52 mmol), morpholine (0.92 g, 10.5 mmol) and sodium tert-butoxide (0.94 g, 9.78 mmol) in toluene (90 ml) and the mixture is degassed and flushed with argon for 45 min. Tris(dibenzylideneacetone)-dipalladium(0) (344 mg, 0.38 mmol) is added and the mixture is heated at 120° C. for 16 h. The mixture is cooled to room temperature and diluted with water (50 ml). The mixture is extracted with ethyl acetate (2×30 ml). The combined organic layers are washed with water (30 ml), brine (40 ml), dried over anhydrous sodium sulfate and evaporated to get the crude which is purified by column chromatography (silica gel, 5% ethyl acetate/dichloromethane) to yield N-[(4-chlorophenyl)-methyl]-2-fluoro-6-methoxy-4-morpholin-4-yl-benzamide (1.3 g, 3.2 mmol, 33%).

Aufarbeitung

  1. customthe mixture is degassed
  2. customflushed with argon for 45 min
  3. temperatureThe mixture is cooled to room temperature
  4. extractionThe mixture is extracted with ethyl acetate (2×30 ml)
  5. washThe combined organic layers are washed with water (30 ml), brine (40 ml)
  6. dry with materialdried over anhydrous sodium sulfate
  7. customevaporated
  8. customto get the crude which
  9. customis purified by column chromatography (silica gel, 5% ethyl acetate/dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-99c16311cd5f4bf3abafe82c16ed8bf9
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09108936B2

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