Hydrochloric Acid → 5-Bromoisoindoline

HRID 41419Notes

Reaction equation

HRID 41419 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=O)[NH:8][C:6](=O)[C:5]2=[CH:11][CH:12]=1.CO.Cl>C1COCC1.O>[Br:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:11][CH:12]=1)[CH2:6][NH:8][CH2:9]2

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 2360184-Bromophthalimide

Product 1

HCID 147958715-BromoisoindolineYield 38.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

280 ml of 1M Borane-THF complex was added dropwise to a stirred solution of 4-bromophthalimide (20.85 g; 92.2 mmol) in anhydrous THF (200 ml) at 0° C. then heated at reflux overnight. The reaction was cooled to 0° C. then treated cautiously with methanol (100 ml) followed by 2M HCl (100 ml) then heated at reflux for 3 hours. The reaction mixture was cooled and the organics evaporated. The aqueous was diluted with water (100 ml) the extracted with DCM (×3). The aqueous was basified with 2M NaOH then extracted with DCM (×3). The combined DCM extracts were dried (MgSO4), filtered and evaporated to give 6.99 g of 5-bromo-2,3-dihydro-1H-isoindole as a dark brown gummy solid. 1H NMR (DMSO-d6) 7.45 (1H, s), 7.36 (1H, d), 7.20 (1H, d), 4.05 (4H, s).

Workup

  1. temperaturethen heated
  2. temperatureat reflux overnight
  3. temperaturethen heated
  4. temperatureat reflux for 3 hours
  5. temperatureThe reaction mixture was cooled
  6. extractionextracted with DCM (×3)
  7. extractionthen extracted with DCM (×3)
  8. dry with materialThe combined DCM extracts were dried (MgSO4)
  9. filtrationfiltered
  10. customevaporated

Sources & evidence

ORD record
ord-7809e5b8d8d84233b0a4a58db03528d5
Source dataset
uspto-grants-2013_09
Patent number
US08530469B2

Reaction notes

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