Cerium(III) chloride → (3aRS,4RS,7aRS)-7,7-dimethyl-4-(2-methoxyphenyl)-2-[(2-methoxyphenyl)acetyl]-4-perhydroisoindolol

HRID 55404

Reaction equation

HRID 55404 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[Mg]Br.[CH3:11][C:12]1([CH3:33])[CH:20]2[CH:16]([CH2:17][N:18]([C:21](=[O:31])[CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[O:29][CH3:30])[CH2:19]2)[C:15](=[O:32])[CH2:14][CH2:13]1.[Cl-].[Ce+3].[Cl-].[Cl-].[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C>[CH3:11][C:12]1([CH3:33])[CH:20]2[CH:16]([CH2:17][N:18]([C:21](=[O:31])[CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[O:29][CH3:30])[CH2:19]2)[C:15]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[O:2][CH3:1])([OH:32])[CH2:14][CH2:13]1

Participants

7

Reactant 4

HCID 24636Cerium(III) chlorideHCID 25517Ammonium ChlorideHCID 67714209(3aRS,7aRS)-7,7-dimethyl-2-[(2-methoxyphenyl)acetyl]-4-perhydroisoindoloneHCID 178489560HCID 178489560, compound

Product 1

HCID 67714347(3aRS,4RS,7aRS)-7,7-dimethyl-4-(2-methoxyphenyl)-2-[(2-methoxyphenyl)acetyl]-4-perhydroisoindololYield 10.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
15 °C

Procedure

To a suspension of 2.61 g of 2-methoxyphenylmagnesium bromide in 10 cm3 of tetrahydrofuran, cooled to 15° C., is added, dropwise and with stirring, a solution of 1.3 g of (3aRS,7aRS)-7,7-dimethyl-2-[(2-methoxyphenyl)acetyl]-4-perhydroisoindolone in 30 cm3 of tetrahydrofuran, followed by 2 g of anhydrous cerium chloride. The reaction mixture is stirred at room temperature for 18 hours, treated with 80 cm3 of saturated aqueous ammonium chloride solution, taken up in 100 cm3 of ethyl acetate and washed with 100 cm3 of 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 silica gel (particle size 0.04-0.06 mm, diameter 3.6 cm, height 22 cm), eluting under a pressure of 0.5 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (70/30 by volume) and collecting 50 cm3 fractions. Fractions 47 to 54 are combined and then concentrated to dryness under reduced pressure (2.5 kPa). The residue is crystallized in 1 cm3 of acetonitrile. 0.177 g of (3aRS,4RS,7aRS)-7,7-dimethyl-4-(2-methoxyphenyl)-2-[(2-methoxyphenyl)acetyl]-4-perhydroisoindolol is obtained, in the form of white crystals melting at 187° C.

Workup

  1. additionis added
  2. stirringThe reaction mixture is stirred at room temperature for 18 hours
  3. washwashed with 100 cm3 of 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 silica gel (particle size 0.04-0.06 mm, diameter 3.6 cm, height 22 cm)
  9. washeluting under a pressure of 0.5 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (70/30 by volume)
  10. customcollecting 50 cm3 fractions
  11. concentrationconcentrated to dryness under reduced pressure (2.5 kPa)
  12. customThe residue is crystallized in 1 cm3 of acetonitrile

Sources & evidence

ORD record
ord-376d50ea7dd34e06ad828a48de35ad27
Source dataset
uspto-grants-1997_04
Patent number
US05624950

Linked notes

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