N-bromobutanimide → 7-bromo-5,8-dichloro-3,4-dihydroisoquinolin-1(2H)-one

HRID 577501Notes

Reaction equation

HRID 577501 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][C:9]([Cl:12])=[C:8]2[C:3]=1[CH2:4][CH2:5][NH:6][C:7]2=[O:13].[Br:14]N1C(=O)CCC1=O>S(=O)(=O)(O)O>[Br:14][C:10]1[C:9]([Cl:12])=[C:8]2[C:3]([CH2:4][CH2:5][NH:6][C:7]2=[O:13])=[C:2]([Cl:1])[CH:11]=1

Participants

4

Reactant 2

HCID 67184N-bromobutanimide2×HCID 867237265,8-dichloro-3,4-dihydroisoquinolin-1(2H)-one

Product 1

HCID 867237277-bromo-5,8-dichloro-3,4-dihydroisoquinolin-1(2H)-oneYield 75%

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent

Procedure

To a solution of 5,8-dichloro-3,4-dihydroisoquinolin-1(2H)-one (253e, 40 g, 0.186 mol) in concentrated sulfuric acid (200 mL) at 60° C. was added N-bromosuccinimide (49.7 g, 0.279 mol) in portions. Stirring was continued at 60° C. for 2 hours, then more N-bromosuccinimide (5 g. 28 mmol) was added. After stirring at 60° C. for 1 hour more, the mixture was poured onto ice water (500 mL), then extracted with dichloromethane (3×500 mL). The combined organic extracts were washed with saturated aqueous sodium chloride solution (800 mL), dried over sodium sulfate, and concentrated in vacuo. The residue was stirred in ethyl acetate (40 mL) and petroleum ether (20 mL), and the resulting solids collected by filtration and dried under vacuum to give 7-bromo-5,8-dichloro-3,4-dihydroisoquinolin-1(2H)-one (253f, 41 g, 75% yield) as an off-white solid.

Workup

  1. stirringAfter stirring at 60° C. for 1 hour more
  2. additionthe mixture was poured onto ice water (500 mL)
  3. extractionextracted with dichloromethane (3×500 mL)
  4. washThe combined organic extracts were washed with saturated aqueous sodium chloride solution (800 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. stirringThe residue was stirred in ethyl acetate (40 mL)
  8. filtrationpetroleum ether (20 mL), and the resulting solids collected by filtration
  9. customdried under vacuum

Sources & evidence

ORD record
ord-f61f677213694c14a5728467e6a52853
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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