Hydrogen Bromide → 5-Chloroisoindoline hydrochloride

HRID 2412169Notes

Reaction equation

HRID 2412169 reaction equation
C1(C)C=CC(S([N:10]2[CH2:18][C:17]3[C:12](=[CH:13][CH:14]=[C:15]([Cl:19])[CH:16]=3)[CH2:11]2)(=O)=O)=CC=1.C1(O)C=CC=CC=1.Br.C(O)(=O)CC>O>[ClH:19].[Cl:19][C:15]1[CH:16]=[C:17]2[C:12](=[CH:13][CH:14]=1)[CH2:11][NH:10][CH2:18]2

Participants

6

Reactant 4

HCID 260Hydrogen BromideHCID 996PhenolHCID 1032Propionic AcidHCID 151678915-Chloro-2-tosylisoindoline

Product 1

HCID 498535025-Chloroisoindoline hydrochlorideYield 97.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

1.0 g of 2-(p-toluensulphonyl)-5-chloroisoindoline and 1.0 g of phenol were added to a mixture of 8 ml of 48% hydrobromic acid and 1.4 ml of propionic acid, and then mixture was heated at reflux for 6 hours. The resultant reaction mixture was diluted with 10 ml of water and extracted twice with 50 ml of ethyl acetate. The water layer was basified with aqueous sodium hydroxide solution and extracted with ethyl acetate three times. The extract was concentrated and the crude product was diluted with 4N HCl/dioxane and stirred for 15 minutes before evaporating the HCl and then re-evaporating with toluene three times to give 0.3 g of 5-chloro-2,3-dihydro-1H-isoindole hydrochloride as a black solid. MS: [M+H]+ 153-15

Workup

  1. temperaturemixture was heated
  2. temperatureat reflux for 6 hours
  3. customThe resultant reaction mixture
  4. extractionextracted twice with 50 ml of ethyl acetate
  5. extractionextracted with ethyl acetate three times
  6. concentrationThe extract was concentrated
  7. additionthe crude product was diluted with 4N HCl/dioxane
  8. custombefore evaporating the HCl
  9. customre-evaporating with toluene three times

Sources & evidence

ORD record
ord-73dc30079b8041469dea7c81fca3bc05
Source dataset
uspto-grants-2014_08
Patent number
US08816087B2

Reaction notes

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