Potassium Carbonate → (3aRS,7aRS)-2-benzyl-7,7-bis(2-fluorophenyl)perhydro-4-isoindolone

HRID 1196242Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1196242
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])[CH2:13][CH2:12][C:11](=[O:14])[CH:10]=[CH:9]1.C(O[CH2:27][N:28]([CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[CH2:29][Si](C)(C)C)CCC.C(=O)([O-])[O-].[K+].[K+]>FC(F)(F)C(O)=O.ClCCl>[CH2:34]([N:28]1[CH2:29][CH:10]2[CH:9]([C:8]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[F:21])([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[F:1])[CH2:13][CH2:12][C:11]2=[O:14])[CH2:27]1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 11097910N-Benzyl-1-butoxy-N-[(trimethylsilyl)methyl]methanamine2×HCID 543727024,4-Bis(2-fluorophenyl)cyclohexenone

Produkt 1

HCID 67915773(3aRS,7aRS)-2-benzyl-7,7-bis(2-fluorophenyl)perhydro-4-isoindolone

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6422Trifluoroacetic acidKatalysator2×HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Trifluoroacetic acid (3 drops) is added to a solution of 4,4-bis(2-fluorophenyl)cyclohexenone (4.3 g) and N-butoxymethyl-N-(trimethylsilylmethyl)benzylamine (5.8 cc) in dry dichloromethane (30 cc). The reaction mixture is brought to reflux and then stirred for 16 hours after the temperature has been allowed to return to 25° C. N-Butoxymethyl-N-(trimethylsilylmethyl)benzylamine (2.5 cc) and trifluoroacetic acid (3 drops) are added and the mixture is stirred for 3 hours under reflux. The reaction mixture is treated with potassium carbonate (3 g) and stirred for 15 minutes. After filtration and concentration to dryness under reduced pressure (2.7 kPa), the residue is chromatographed on a column of silica gel (particle size 0.04-0.063 mm, diameter 4 cm, height 32 cm), eluting under a nitrogen pressure of 0.5 bar with a mixture of cyclohexane and ethyl acetate (85:15) and collecting 20-cc fractions. Fractions 13 to 22 are combined and concentrated to dryness under reduced pressure (2.7 kPa) to give (3aRS,7aRS)-2-benzyl-7,7-bis(2-fluorophenyl)perhydro-4-isoindolone (2.28 g). M.p. 138° C.

Aufarbeitung

  1. temperatureto reflux
  2. customto return to 25° C
  3. stirringthe mixture is stirred for 3 hours
  4. temperatureunder reflux
  5. stirringstirred for 15 minutes
  6. filtrationAfter filtration and concentration to dryness under reduced pressure (2.7 kPa)
  7. customthe residue is chromatographed on a column of silica gel (particle size 0.04-0.063 mm, diameter 4 cm, height 32 cm)
  8. washeluting under a nitrogen pressure of 0.5 bar
  9. additionwith a mixture of cyclohexane and ethyl acetate (85:15)
  10. customcollecting 20-cc fractions
  11. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Quellen und Nachweise

ORD-Eintrag
ord-af698ee581b9495897ee9627a6576c20
Quelldatensatz
uspto-grants-1992_05
Patentnummer
US05112988

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