Methyl 3-[4-(aminomethyl)phenyl]propionate → 6-bromo-2-[4-(2-methoxycarbonylethyl)benzyl]-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic Acid Methyl Ester

HRID 750299Notes

Reaction equation

HRID 750299 reaction equation
[CH3:1][O:2][C:3]([C:5]1[O:6][C:7]([C:9]2[C:14]([C:15]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[CH:13][C:12]([Br:22])=[CH:11][CH:10]=2)=O)=[O:4].[CH3:23][O:24][C:25](=[O:36])[CH2:26][CH2:27][C:28]1[CH:33]=[CH:32][C:31]([CH2:34][NH2:35])=[CH:30][CH:29]=1>CO>[CH3:1][O:2][C:3]([C:5]1[N:35]([CH2:34][C:31]2[CH:32]=[CH:33][C:28]([CH2:27][CH2:26][C:25]([O:24][CH3:23])=[O:36])=[CH:29][CH:30]=2)[C:7](=[O:6])[C:9]2[C:14]([C:15]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[CH:13][C:12]([Br:22])=[CH:11][CH:10]=2)=[O:4]

Participants

4

Reactant 2

HCID 413297Methyl 3-[4-(aminomethyl)phenyl]propionateHCID 66990710Methyl 6-bromo-1-oxo-4-phenyl-1H-isochromene-3-carboxylate

Product 1

HCID 691572426-bromo-2-[4-(2-methoxycarbonylethyl)benzyl]-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic Acid Methyl EsterYield 80%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 6-bromo-4-phenyl-3-isocoumarincarboxylic acid methyl ester (359 mg) in methanol (20 ml) was added 3-(4-aminomethylphenyl)propionic acid methyl ester (387 mg) and the mixture was stirred at room temperature for 18 hr. The solvent was evaporated under reduced pressure, 1N hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried by adding sodium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was dissolved in methanol (30 ml) and conc. sulfuric acid (3 ml) was added. The mixture was heated under reflux for 3 hrs. The solvent was evaporated under reduced pressure, water was added under ice-cooling and the mixture was neutralized with potassium carbonate. The solution was extracted with ethyl acetate. The extract was washed with saturated brine and dried by adding sodium sulfate. The obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=19/1→3/1) to give the title compound (425 mg, 80%).

Workup

  1. customThe solvent was evaporated under reduced pressure, 1N hydrochloric acid
  2. additionwas added
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. customdried
  6. additionby adding sodium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. dissolutionthe obtained residue was dissolved in methanol (30 ml)
  9. additionconc. sulfuric acid (3 ml) was added
  10. temperatureThe mixture was heated
  11. temperatureunder reflux for 3 hrs
  12. customThe solvent was evaporated under reduced pressure, water
  13. additionwas added under ice-
  14. temperaturecooling
  15. extractionThe solution was extracted with ethyl acetate
  16. washThe extract was washed with saturated brine
  17. customdried
  18. additionby adding sodium sulfate
  19. customThe obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=19/1→3/1)

Sources & evidence

ORD record
ord-f3c6d0f5f79e4b42b4ea0f0b0c289696
Source dataset
uspto-grants-2008_07
Patent number
US07402595B2

Reaction notes

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