Phenol → 5-Bromo-1-methyl-2,3-dihydro-1H-isoindole

HRID 1061451Notes

Reaction equation

HRID 1061451 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH:7]([CH3:11])[N:6](S(C1C=CC(C)=CC=1)(=O)=O)[CH2:5]2.C1(O)C=CC=CC=1.C(O)(=O)CC.[H-].[Na+]>Br>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH:7]([CH3:11])[NH:6][CH2:5]2

Participants

6

Reactant 4

HCID 996PhenolHCID 1032Propionic AcidHCID 24758Sodium hydrideHCID 53642132HCID 53642132, compound

Product 1

HCID 184018095-Bromo-1-methyl-2,3-dihydro-1H-isoindoleYield 89.7%

Reagents, catalysts & solvents 1

HCID 260Hydrogen BromideSolvent

Procedure

67.46 g of 5-bromo-1-methyl-2-(p-toluene sulfonyl)isoindoline (3-8) was suspended in 325 ml of 47% hydrobromic acid and 48 ml of phenol and 197 ml of propionic acid were added thereto and the resulting mixture was heated under reflux for 4 hours. After the reaction was completed, the reaction mixture was adjusted to be alkaline with 8N sodium hydride solution and extracted with chloroform and the resulting organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the resulting residue was purified by silica gel chromatopraphy (eluent; chloroform:methanol=19:1) to obtain 35.03 g of 5-bromo-1-methylisoindoline.

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureunder reflux for 4 hours
  3. extractionextracted with chloroform
  4. dry with materialthe resulting organic layer was dried over anhydrous magnesium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customthe resulting residue was purified by silica gel chromatopraphy (eluent; chloroform:methanol=19:1)

Sources & evidence

ORD record
ord-de430c6e0f094d54a5f5526540581a0b
Source dataset
uspto-grants-2003_02
Patent number
US06525066B2

Reaction notes

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