Ammonium Chloride → (3aRS,4RS,5RS,7aSR)-2-benzyl-4-(2-methoxyphenyl)-5methyl-4-perhydroisoindolol

HRID 55419Notes

Reaction equation

HRID 55419 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[Mg]Br.[CH2:11]([N:18]1[CH2:26][CH:25]2[CH:20]([CH2:21][CH2:22][CH:23]([CH3:28])[C:24]2=[O:27])[CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C>[CH2:11]([N:18]1[CH2:26][CH:25]2[CH:20]([CH2:21][CH2:22][CH:23]([CH3:28])[C:24]2([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[O:2][CH3:1])[OH:27])[CH2:19]1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 67714068(3aRS,5RS,7aSR)-2benzyl-5-methyl-4-perhydroisoindoloneHCID 178489560HCID 178489560, compound

Product 1

HCID 67714049(3aRS,4RS,5RS,7aSR)-2-benzyl-4-(2-methoxyphenyl)-5methyl-4-perhydroisoindololYield 98.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 2.13 g of 2-methoxyphenylmagnesium bromide in 15 cm3 of tetrahydrofuran is added dropwise, at room temperature and with stirring, a solution of 0.7 g of (3aRS,5RS,7aSR)-2-benzyl-5-methyl-4-perhydroisoindolone in 15 cm3 of tetrahydrofuran. The reaction mixture is stirred at room temperature for 48 hours, treated with 50 cm3 of saturated aqueous ammonium chloride solution, taken up in ethyl acetate and washed with saturated aqueous sodium chloride solution. The organic phase is separated out after settling has taken place, dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a column of Merck silica gel (particle size 0.04-0.06 mm, diameter 2 cm, height 15 cm), eluting under a pressure of 0.5 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (60/40 by volume) and collecting 25 cm3 fractions. Fractions 10 to 20 are combined and then concentrated to dryness under reduced pressure (2.5 kPa). 1 g of (3aRS,4RS,5RS,7aSR)-2-benzyl-4-(2-methoxyphenyl)-5methyl-4-perhydroisoindolol is obtained in the form of a yellow oil.

Workup

  1. additionis added dropwise, at room temperature
  2. stirringThe reaction mixture is stirred at room temperature for 48 hours
  3. washwashed with saturated aqueous sodium chloride solution
  4. customThe organic phase is separated out after settling
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  8. customThe residue is chromatographed on a column of Merck silica gel (particle size 0.04-0.06 mm, diameter 2 cm, height 15 cm)
  9. washeluting under a pressure of 0.5 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (60/40 by volume)
  10. customcollecting 25 cm3 fractions
  11. concentrationconcentrated to dryness under reduced pressure (2.5 kPa)

Sources & evidence

ORD record
ord-9547b6fd8997453899b6b6abcf62c27d
Source dataset
uspto-grants-1997_04
Patent number
US05624950

Reaction notes

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