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

HRID 55402

Reaction equation

HRID 55402 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[Mg]Br.C([O:14][CH:15]1[CH2:23][CH2:22][CH:21]2[CH:17]([CH2:18][N:19]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH2:20]2)[C:16]1=[O:31])(=O)C.[Cl-].[NH4+]>O1CCCC1.C(OCC)C>[CH2:24]([N:19]1[CH2:18][CH:17]2[CH:21]([CH2:22][CH2:23][CH:15]([OH:14])[C:16]2([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[O:2][CH3:1])[OH:31])[CH2:20]1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 67714196(3aRS,5RS,7aSR)-5-acetoxy-2-benzyl-4-perhydroisoindoloneHCID 178489560HCID 178489560, compound

Product 1

HCID 67713929(3aRS,4RS,5RS,7aSR)-2-benzyl-4-(2-methoxyphenyl)-4,5-perhydroisoindolediolYield 26.8%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of 27.6 g of 2-methoxyphenylmagnesium bromide in 60 cm' of tetrahydrofuran are added dropwise, at room temperature and with stirring, a solution of 4.7 g of (3aRS,5RS,7aSR)-5-acetoxy-2-benzyl-4-perhydroisoindolone in 90 cm3 of tetrahydrofuran. The reaction mixture is stirred at room temperature for 3 hours, treated with 200 cm3 of saturated aqueous ammonium chloride solution and taken up in 200 cm3 of ethyl ether and 100 g of ice. 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 crystallized in 80 cm3 of petroleum ether and then chromatographed on a column of silica gel (particle size 0.04-0.06 mm, diameter 1 cm, height 20 cm), eluting under a pressure of 0.5 bar of nitrogen with a mixture of dichloromethane and methanol (95/5 by volume) and collecting 25 cm3 fractions. Fractions 14 to 21 are combined and then concentrated to dryness under reduced pressure (2.5 kPa). 1.55 g of (3aRS,4RS,5RS,7aSR)-2-benzyl-4-(2-methoxyphenyl)-4,5-perhydroisoindolediol are obtained, melting at 140° C.

Workup

  1. additionare added dropwise, at room temperature
  2. stirringThe reaction mixture is stirred at room temperature for 3 hours
  3. customThe organic phase is separated out after settling
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  7. customThe residue is crystallized in 80 cm3 of petroleum ether
  8. customchromatographed on a column of silica gel (particle size 0.04-0.06 mm, diameter 1 cm, height 20 cm)
  9. washeluting under a pressure of 0.5 bar of nitrogen with a mixture of dichloromethane and methanol (95/5 by volume)
  10. customcollecting 25 cm3 fractions
  11. concentrationconcentrated to dryness under reduced pressure (2.5 kPa)

Sources & evidence

ORD record
ord-67d3926d58e94c3b98873508a730e72e
Source dataset
uspto-grants-1997_04
Patent number
US05624950

Linked notes

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