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

HRID 1029940ノート

反応式

HRID 1029940 の反応式
[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

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6422Trifluoroacetic acid触媒2 回HCID 6344Dichloromethane溶媒

実験手順

Trifluoroacetic acid (3 drops) is added to a solution of 4,4-bis-(2-fluorophenyl)-cyclohexenone (4.3 g) and N-butoxymethyl-N-trimethylsilylmethylbenzylamine (5.8 cc) in dry dichloromethane (30 cc). The reaction mixture is brought to reflux and then stirred for 16 hours after having allowed the temperature to return to 25° C. N-Butoxymethyl-N-trimethylsilymethylbenzylamine (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 filtering and concentrating the filtrate to dryness under reduced pressure (2.7 kPa), the residue is chromatographed on a silica gel column (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)-4-perhydroisoindolone (2.28 g). m.p.=138° C.

後処理

  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 filtering
  7. concentrationconcentrating the filtrate to dryness under reduced pressure (2.7 kPa)
  8. customthe residue is chromatographed on a silica gel column (particle size 0.04-0.063 mm, diameter 4 cm, height 32 cm)
  9. washeluting under a nitrogen pressure of 0.5 bar
  10. additionwith a mixture of cyclohexane and ethyl acetate (85/15)
  11. customcollecting 20 cc fractions
  12. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

出典と根拠

ORDレコード
ord-48a3dd802f2544478b62f0f74d6dd849
出典データセット
uspto-grants-1992_04
特許番号
US05102667

反応ノート

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