Ammonium Chloride → methyl (3aRS,4SR,7RS,7aRS)-2-benzyl-7-hydroxy-7-[4-(trifluoromethyl)phenyl]-4-phenyloctahydroisoindole-3a-carboxylate

HRID 849599Notes

Reaction equation

HRID 849599 reaction equation
[Mg].[F:2][C:3]([F:12])([F:11])[C:4]1[CH:9]=[CH:8][C:7](Br)=[CH:6][CH:5]=1.[CH3:13][O:14][C:15]([C:17]12[CH:25]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:24][CH2:23][C:22](=[O:32])[CH:21]1[CH2:20][N:19]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[CH2:18]2)=[O:16].[Cl-].[NH4+]>C(OCC)C>[CH3:13][O:14][C:15]([C:17]12[CH:25]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH2:24][CH2:23][C:22]([OH:32])([C:7]3[CH:8]=[CH:9][C:4]([C:3]([F:12])([F:11])[F:2])=[CH:5][CH:6]=3)[CH:21]1[CH2:20][N:19]([CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)[CH2:18]2)=[O:16]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 5462224MagnesiumHCID 11302988methyl(3aRS,4SR,7aRS)-2-benzyl-7-oxo-4-phenyloctahydroisoindole-3a-carboxylate

Product 1

HCID 86755051methyl (3aRS,4SR,7RS,7aRS)-2-benzyl-7-hydroxy-7-[4-(trifluoromethyl)phenyl]-4-phenyloctahydroisoindole-3a-carboxylateYield 66.2%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
10 °C

Procedure

0.8 g of magnesium turnings was added to a solution of 7.2 g of 4-(trifluoromethyl)bromobenzene in 40 cm3 of dry diethyl ether. The reaction mixture was spontaneously brought to reflux for ten minutes and was then heated at reflux for twenty minutes. The reaction mixture was subsequently cooled and a solution of 5.6 g of methyl(3aRS,4SR,7aRS)-2-benzyl-7-oxo-4-phenyloctahydroisoindole-3a-carboxylate in 40 cm3 of dry diethyl ether was added over fifteen minutes at a temperature in the region of 10° C. The reaction mixture was stirred for ten minutes at a temperature in the region of 10° C. and then poured into 150 cm3 of a saturated aqueous ammonium chloride solution. The aqueous phase was separated by settling and extracted with three times 75 cm3 of diethyl ether. The organic phases were combined, washed successively with three times 75 cm3 of distilled water, dried over magnesium sulphate in the presence of 3S charcoal and concentrated under reduced pressure. After crystallization from 25 cm3 of pentane, 5.2 g of methyl(3aRS,4SR,7RS,7aRS)-2-benzyl-7-hydroxy-7-[4-(trifluoromethyl)phenyl]-4-phenyloctahydroisoindole-3a-carboxylate were obtained in the form of a beige solid, the characteristic of which was as follows:

Workup

  1. temperatureto reflux for ten minutes
  2. temperaturewas then heated
  3. temperatureat reflux for twenty minutes
  4. temperatureThe reaction mixture was subsequently cooled
  5. customThe aqueous phase was separated
  6. extractionextracted with three times 75 cm3 of diethyl ether
  7. washwashed successively with three times 75 cm3 of distilled water
  8. dry with materialdried over magnesium sulphate in the presence of 3S charcoal
  9. concentrationconcentrated under reduced pressure
  10. customAfter crystallization from 25 cm3 of pentane

Sources & evidence

ORD record
ord-d9e67cd0f849411fa36592f3ca5a11f1
Source dataset
uspto-grants-2000_01
Patent number
US06013662

Reaction notes

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