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

HRID 1196242노트

반응식

HRID 1196242 반응식
[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

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 11097910N-Benzyl-1-butoxy-N-[(trimethylsilyl)methyl]methanamine2회HCID 543727024,4-Bis(2-fluorophenyl)cyclohexenone

생성물 1

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

시약·촉매·용매 2

HCID 6422Trifluoroacetic acid촉매2회HCID 6344Dichloromethane용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-af698ee581b9495897ee9627a6576c20
출처 데이터셋
uspto-grants-1992_05
특허 번호
US05112988

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