tert-Butyl 2-(aminomethyl)piperidine-1-carboxylate → 6-bromo-2-(1-tert-butoxycarbonylpiperidin-2-ylmethyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic Acid Methyl Ester

HRID 750139Notes

Reaction equation

HRID 750139 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].[C:23]([O:27][C:28]([N:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH:31]1[CH2:36][NH2:37])=[O:29])([CH3:26])([CH3:25])[CH3:24]>CO>[CH3:1][O:2][C:3]([C:5]1[N:37]([CH2:36][CH:31]2[CH2:32][CH2:33][CH2:34][CH2:35][N:30]2[C:28]([O:27][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:29])[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 2756482tert-Butyl 2-(aminomethyl)piperidine-1-carboxylateHCID 66990710Methyl 6-bromo-1-oxo-4-phenyl-1H-isochromene-3-carboxylate

Product 1

HCID 691559506-bromo-2-(1-tert-butoxycarbonylpiperidin-2-ylmethyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic Acid Methyl EsterYield 12%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 6-bromo-4-phenyl-3-isocoumarincarboxylic acid methyl ester (539 mg) in methanol (10 ml) was added 2-aminomethylpiperidine-1-carboxylic acid tert-butyl ester (1.07 g), and the mixture was stirred at room temperature for 12 hrs. 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 4N hydrogen chloride-ethyl acetate solution (5 ml) was added to the obtained residue. The mixture was stirred at room temperature for 10 hrs. The solvent was evaporated under reduced pressure, and 1N aqueous sodium hydroxide solution (10 ml), tetrahydrofuran (10 ml) and di-tert-butyl carbonate (437 mg) were added. The mixture was stirred at room temperature for 12 hrs. The solvent was evaporated under reduced pressure, and the obtained residue 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=9/1→4/1) to give the title compound (64 mg, 12%).

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, and 4N hydrogen chloride-ethyl acetate solution (5 ml)
  8. additionwas added to the obtained residue
  9. stirringThe mixture was stirred at room temperature for 10 hrs
  10. customThe solvent was evaporated under reduced pressure, and 1N aqueous sodium hydroxide solution (10 ml), tetrahydrofuran (10 ml) and di-tert-butyl carbonate (437 mg)
  11. additionwere added
  12. stirringThe mixture was stirred at room temperature for 12 hrs
  13. customThe solvent was evaporated under reduced pressure
  14. extractionthe obtained residue was extracted with ethyl acetate
  15. washThe extract was washed with saturated brine
  16. customdried
  17. additionby adding sodium sulfate
  18. customThe obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=9/1→4/1)

Sources & evidence

ORD record
ord-888b196aa3b74bef8505a89d358e4050
Source dataset
uspto-grants-2008_07
Patent number
US07402595B2

Reaction notes

Loading…