Ammonium Chloride → methyl (3aRS,4SR,7RS,7aRS)-2-benzyl-7-hydroxy-7-(3,4-dimethylphenyl)-4-phenyl-octahydroisoindole-3a-carboxylate

HRID 1955403Notes

Reaction equation

HRID 1955403 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH3:9])[C:5]([CH3:8])=[CH:6][CH:7]=1.[Mg].[CH2:11]([N:18]1[CH2:26][C:25]2([C:27]([O:29][CH3:30])=[O:28])[CH:20]([C:21](=[O:37])[CH2:22][CH2:23][CH:24]2[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[Cl-].[NH4+]>C(OCC)C.O1CCCC1>[CH2:11]([N:18]1[CH2:26][C:25]2([C:27]([O:29][CH3:30])=[O:28])[CH:20]([C:21]([OH:37])([C:2]3[CH:7]=[CH:6][C:5]([CH3:8])=[C:4]([CH3:9])[CH:3]=3)[CH2:22][CH2:23][CH:24]2[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 685044-Bromo-o-xyleneHCID 5462224MagnesiumHCID 11302988methyl(3aRS,4SR,7aRS)-2-benzyl-7-oxo-4-phenyloctahydroisoindole-3a-carboxylate

Product 1

HCID 86755048methyl (3aRS,4SR,7RS,7aRS)-2-benzyl-7-hydroxy-7-(3,4-dimethylphenyl)-4-phenyl-octahydroisoindole-3a-carboxylate

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-7 °C

Procedure

2.3 cm3 of 4-bromo-ortho-xylene and 0.42 g of magnesium turnings in a mixture of 20 cm3 of diethyl ether and 20 cm3 of tetrahydrofuran were heated at reflux for one hour. After cooling to a temperature in the region of -7° C., a solution of 3.11 g of methyl (3aRS,4SR,7aRS)-2-benzyl-7-oxo-4-phenyloctahydroisoindole-3a-carboxylate in 20 cm3 of diethyl ether was added over 25 minutes. The reaction mixture was stirred for four hours at a temperature in the region of 25° C. and then hydrolysed by 50 cm3 of a saturated aqueous ammonium chloride solution. The aqueous phase was separated by settling and extracted with 25 cm3 of ethyl acetate. The organic phases were combined, dried over magnesium sulphate and concentrated under reduced pressure. After purification by flash chromatography on silica gel (230-400 mesh), elution being carried out with a cyclohexane/ethyl acetate (80/20 by volume) mixture, 1.995 g of methyl (3aRS,4SR,7RS,7aRS)-2-benzyl-7-hydroxy-7-(3,4-dimethylphenyl)-4-phenyl-octahydroisoindole-3a-carboxylate were obtained, the characteristic of which compound, used as it was in the following stage, was as follows:

Workup

  1. temperaturewere heated
  2. temperatureat reflux for one hour
  3. customThe aqueous phase was separated
  4. extractionextracted with 25 cm3 of ethyl acetate
  5. dry with materialdried over magnesium sulphate
  6. concentrationconcentrated under reduced pressure
  7. customAfter purification by flash chromatography
  8. washon silica gel (230-400 mesh), elution

Sources & evidence

ORD record
ord-082a8b1822c24489ac93525b5413901e
Source dataset
uspto-grants-2000_09
Patent number
US06124465

Reaction notes

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