Isoquinoline → 5-Bromoisoquinoline

HRID 641921Notes

Reaction equation

HRID 641921 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.C1C(=O)N([Br:18])C(=O)C1>OS(O)(=O)=O>[Br:18][C:6]1[CH:7]=[CH:8][CH:9]=[C:10]2[C:5]=1[CH:4]=[CH:3][N:2]=[CH:1]2

Participants

4

Reactant 2

HCID 8405IsoquinolineHCID 67184N-bromobutanimide

Product 1

HCID 7364875-Bromoisoquinoline

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent

Conditions

Temperature
0 °C

Procedure

Into a 250 mL 3-necked round bottom flask was placed H2SO4 (150 mL). To the above was added isoquinoline (17 g, 131.62 mmol) in several batches, while cooling to a temperature of 0° C. To the above was added NBS (29.2 g, 164.04 mmol) in several batches, while cooling to a temperature of −25-−22° C. The resulting solution was allowed to react, with stirring, for 2 hours while the temperature was maintained at −25-−22° C. The resulting solution was allowed to react, with stirring, overnight while the temperature was maintained at room temperature. The reaction progress was monitored by TLC (ethyl acetate/petroleum ether=1:5). The reaction mixture was then quenched by the adding 1000 mL of H2O/ice. Adjustment of the pH to 8-10 was accomplished by the addition of NH3. H2O (30%). The resulting solution was extracted four times with 500 mL of ethyl acetate and the organic layers combined and dried over Na2SO4. The residue was purified by eluting through a column with a 1:5 ethyl acetate/petroleum ether solvent system. This resulted in 22.24 g (81%) of 5-bromoisoquinoline as a white solid.

Workup

  1. customInto a 250 mL 3-necked round bottom flask was placed
  2. temperaturewhile cooling to a temperature of −25-−22° C
  3. customto react
  4. temperaturewas maintained at −25-−22° C
  5. customto react
  6. stirringwith stirring, overnight while the temperature
  7. temperaturewas maintained at room temperature
  8. customThe reaction mixture was then quenched by the adding 1000 mL of H2O/ice
  9. additionAdjustment of the pH to 8-10 was accomplished by the addition of NH3
  10. extractionThe resulting solution was extracted four times with 500 mL of ethyl acetate
  11. dry with materialdried over Na2SO4
  12. customThe residue was purified
  13. washby eluting through a column with a 1:5 ethyl acetate/petroleum ether solvent system
  14. customThis resulted in 22.24 g (81%) of 5-bromoisoquinoline as a white solid

Sources & evidence

ORD record
ord-32a86c4c1d034bdaaa96be62ce83d181
Source dataset
uspto-grants-2010_04
Patent number
US07696229B2

Reaction notes

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