4-Bromotoluene → methyl (3aRS,4SR,7RS,7aRS)-2-benzyl-7-hydroxy-7-(4-methylphenyl)-4-phenyloctahydroisoindole-3a-carboxylate

HRID 324655Notes

Reaction equation

HRID 324655 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][CH:3]=1.[Mg].[CH2:10]([N:17]1[CH2:25][C:24]2([C:26]([O:28][CH3:29])=[O:27])[CH:19]([C:20](=[O:36])[CH2:21][CH2:22][CH:23]2[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:18]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[Cl-].[NH4+]>C(OCC)C.C1(C)C=CC=CC=1>[CH2:10]([N:17]1[CH2:25][C:24]2([C:26]([O:28][CH3:29])=[O:27])[CH:19]([C:20]([OH:36])([C:2]3[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][CH:3]=3)[CH2:21][CH2:22][CH:23]2[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:18]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

7

Reactant 4

HCID 78054-BromotolueneHCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 11302988methyl(3aRS,4SR,7aRS)-2-benzyl-7-oxo-4-phenyloctahydroisoindole-3a-carboxylate

Product 1

HCID 11328545methyl (3aRS,4SR,7RS,7aRS)-2-benzyl-7-hydroxy-7-(4-methylphenyl)-4-phenyloctahydroisoindole-3a-carboxylate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 3283Diethyl EtherSolvent

Conditions

Temperature
60 °C

Procedure

5.1 cm3 of 4-bromotoluene and 1 g of magnesium turnings in 100 cm3 of diethyl ether were heated at reflux for one hour. 100 cm3 of toluene were added and the mixture was heated to 60° C. under a stream of nitrogen. After cooling to a temperature in the region of 5° C., a solution of 10 g of methyl (3aRS,4SR,7aRS)-2-benzyl-7-oxo-4-phenyloctahydroisoindole-3a-carboxylate in 80 cm3 of toluene was added. The reaction mixture was stirred for one hour at a temperature in the region of 20° C. and then hydrolysed with 100 cm3 of a saturated aqueous ammonium chloride solution. The aqueous phase was separated by settling and extracted with two times 75 cm3 of ethyl acetate. The organic phases were combined, washed successively with 100 cm3 of distilled water and 100 cm3 of a saturated aqueous sodium chloride solution, dried over magnesium sulphate and concentrated under reduced pressure. After purification by flash chromatography on silica gel (230-400 mesh), elution was carried out with a cyclohexane/ethyl acetate (80/20 by volume) mixture, 9 g of methyl (3aRS,4SR,7RS,7aRS)-2-benzyl-7-hydroxy-7-(4-methylphenyl)-4-phenyloctahydroisoindole-3a-carboxylate were obtained in the form of a white solid, the characteristics of which were as follows:

Workup

  1. temperatureat reflux for one hour
  2. temperatureAfter cooling to a temperature in the region of 5° C.
  3. customThe aqueous phase was separated
  4. extractionextracted with two times 75 cm3 of ethyl acetate
  5. washwashed successively with 100 cm3 of distilled water and 100 cm3 of a saturated aqueous sodium chloride solution
  6. dry with materialdried over magnesium sulphate
  7. concentrationconcentrated under reduced pressure
  8. customAfter purification by flash chromatography
  9. washon silica gel (230-400 mesh), elution

Sources & evidence

ORD record
ord-1c1852d9effb4e98a0171022c0a225be
Source dataset
uspto-grants-2001_04
Patent number
US06218406B1

Reaction notes

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