Trifluoroacetic acid → (3aRS,7aSR)-2-benzyl-7,7-dimethoxy-2,3,3a, 4,7,7a-hexahydro-1H-4-isoindolone

HRID 55428Notes

Reaction equation

HRID 55428 reaction equation
[CH3:1][O:2][C:3]1([O:10][CH3:11])[CH:8]=[CH:7][C:6](=[O:9])[CH:5]=[CH:4]1.C(O[CH2:17][N:18]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH2:19][Si](C)(C)C)CCC.FC(F)(F)C(O)=O.C(=O)([O-])[O-].[K+].[K+]>ClCCl>[CH2:24]([N:18]1[CH2:19][CH:7]2[CH:8]([C:3]([O:2][CH3:1])([O:10][CH3:11])[CH:4]=[CH:5][C:6]2=[O:9])[CH2:17]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 3946484,4-Dimethoxy-2,5-cyclohexadien-1-oneHCID 11097910N-Benzyl-1-butoxy-N-[(trimethylsilyl)methyl]methanamine

Product 1

HCID 67714120(3aRS,7aSR)-2-benzyl-7,7-dimethoxy-2,3,3a, 4,7,7a-hexahydro-1H-4-isoindolone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 22.9 g of 4,4-dimethoxy-2,5-cyclohexadien-1-one [J. Org. Chem., 52, 2763 (1987)] and 46 cm3 of N-butoxymethyl-N-trimethylsilylmethylbenzylamine in 150 cm3 of dry dichloromethane are added dropwise 3 cm3 of trifluoroacetic acid. Once the reaction mixture has reached reflux it is allowed to return to room temperature and is then stirred for for one hour. After addition of 5 g of potassium carbonate, the suspension obtained is filtered and the filtrate is concentrated to dryness under reduced pressure (2.7 kPa). The residue obtained is purified by chromatography on a column of silica gel (particle size 0.06-0.20 mm), eluting with a mixture of cyclohexane and ethyl acetate (90/10 then 80/20 by volume). 19 g of (3aRS,7aSR)-2-benzyl-7,7-dimethoxy-2,3,3a, 4,7,7a -hexahydro-1H-4-isoindolone are obtained in oil form.

Workup

  1. temperatureOnce the reaction mixture has reached reflux it
  2. customto return to room temperature
  3. customthe suspension obtained
  4. filtrationis filtered
  5. concentrationthe filtrate is concentrated to dryness under reduced pressure (2.7 kPa)
  6. customThe residue obtained
  7. customis purified by chromatography on a column of silica gel (particle size 0.06-0.20 mm)
  8. washeluting with a mixture of cyclohexane and ethyl acetate (90/10

Sources & evidence

ORD record
ord-e4f6b6e504cc47ce92e656005e8e7f99
Source dataset
uspto-grants-1997_04
Patent number
US05624950

Reaction notes

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