Cesium carbonate → (3S)-1-[4-chloro-2-(trifluoromethyl)phenyl]pyrrolidin-3-ol

HRID 2198055Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2198055
Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[NH:13]1[CH2:17][CH2:16][C@H:15]([OH:18])[CH2:14]1.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.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([N:13]2[CH2:17][CH2:16][C@H:15]([OH:18])[CH2:14]2)=[C:3]([C:9]([F:12])([F:11])[F:10])[CH:4]=1

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 1361722-Bromo-5-chlorobenzotrifluorideHCID 634876Binap, (A+-)-HCID 2733874(3S)-pyrrolidin-3-ol

Produkt 1

HCID 67022292(3S)-1-[4-chloro-2-(trifluoromethyl)phenyl]pyrrolidin-3-olAusbeute 81,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittel

Versuchsvorschrift

A solution of 1-bromo-4-chloro-2-(trifluoromethyl)benzene (15.0 g), (3S)-pyrrolidin-3-ol (5.0 g), palladium(II) acetate (561 mg), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (3.11 g) and cesium carbonate (37.8 g) in toluene (280 ml) was stirred under an argon gas atmosphere at 100° C. for 18 hr. After cooling to room temperature, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate 95:5-80:20) to give the title compound (12.4 g, yield 81%) as a colorless oil.

Aufarbeitung

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated
  6. customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate 95:5-80:20)

Quellen und Nachweise

ORD-Eintrag
ord-ace196af8f554a648528af1e8bc49f79
Quelldatensatz
uspto-grants-2012_12
Patentnummer
US08338622B2

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