2-Bromoanisole → (3aRS,4RS,7SR,7aRS)-7-methyl-7-phenyl-4-(2-methoxyphenyl)-2-[(2-methoxyphenyl)acetyl]-4perhydroisoindolol

HRID 55414Notes

Reaction equation

HRID 55414 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[Mg]Br.[Mg].BrC1C=CC=CC=1OC.[CH3:21][C:22]1([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH:30]2[CH:26]([CH2:27][N:28]([C:31](=[O:41])[CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=3[O:39][CH3:40])[CH2:29]2)[C:25](=[O:42])[CH2:24][CH2:23]1.[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C>[CH3:21][C:22]1([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH:30]2[CH:26]([CH2:27][N:28]([C:31](=[O:41])[CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=3[O:39][CH3:40])[CH2:29]2)[C:25]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[O:2][CH3:1])([OH:42])[CH2:24][CH2:23]1

Participants

8

Reactant 5

HCID 113582-BromoanisoleHCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 67714033(3aRS,7SR,7aRS)-7-methyl-7-phenyl-2-[(2methoxyphenyl)acetyl]-4-perhydroisoindoloneHCID 178489560HCID 178489560, compound

Product 1

HCID 67714239(3aRS,4RS,7SR,7aRS)-7-methyl-7-phenyl-4-(2-methoxyphenyl)-2-[(2-methoxyphenyl)acetyl]-4perhydroisoindolol

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
30 °C

Procedure

To a suspension of 2-methoxyphenylmagnesium bromide, prepared from 0,576 g of magnesium and 4.5 g of 2-bromoanisole in 25 cm3 of tetrahydrofuran, is added dropwise, with stirring and at 30° C., a solution of 1.6 g of (3aRS,7SR,7aRS)-7-methyl-7-phenyl-2-[(2methoxyphenyl)acetyl]-4-perhydroisoindolone in 40 cm3 of tetrahydrofuran. The reaction mixture is stirred at room temperature for 18 hours, treated with 100 cm3 of saturated aqueous ammonium chloride solution, taken up in 100 cm3 of ethyl acetate and washed with 100 cm3 of water and then 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 cm, height 16 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 35 cm3 fractions. Fractions 8 to 16 are combined and then concentrated to dryness under reduced pressure (2.5 kPa). The residue is crystallized in 4 cm3 of ethyl acetate. 0.6 g of (3aRS,4RS,7SR,7aRS)-7-methyl-7-phenyl-4-(2-methoxyphenyl)-2-[(2-methoxyphenyl)acetyl]-4perhydroisoindolol is obtained, in the form of white crystals melting at 234° C.

Workup

  1. additionis added dropwise
  2. stirringThe reaction mixture is stirred at room temperature for 18 hours
  3. washwashed with 100 cm3 of water
  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 cm, height 16 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 35 cm3 fractions
  11. concentrationconcentrated to dryness under reduced pressure (2.5 kPa)
  12. customThe residue is crystallized in 4 cm3 of ethyl acetate

Sources & evidence

ORD record
ord-133859a8aac847aaaf7d8f1c1923191e
Source dataset
uspto-grants-1997_04
Patent number
US05624950

Reaction notes

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