Sodium hydride → 6-bromo-2-(3-methoxycarbonylbenzyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic Acid Methyl Ester

HRID 750133Notes

Reaction equation

HRID 750133 reaction equation
[CH3:1][O:2][C:3]([C:5]1[NH:6][C:7](=[O:22])[C:8]2[C:13]([C:14]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[CH:12][C:11]([Br:21])=[CH:10][CH:9]=2)=[O:4].[H-].[Na+].[CH3:25][O:26][C:27](=[O:36])[C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([CH2:34]Br)[CH:29]=1>CN(C)C=O>[CH3:1][O:2][C:3]([C:5]1[N:6]([CH2:34][C:30]2[CH:31]=[CH:32][CH:33]=[C:28]([C:27]([O:26][CH3:25])=[O:36])[CH:29]=2)[C:7](=[O:22])[C:8]2[C:13]([C:14]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[CH:12][C:11]([Br:21])=[CH:10][CH:9]=2)=[O:4]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 517981Methyl 3-(bromomethyl)benzoateHCID 691573826-bromo-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic Acid Methyl Ester

Product 1

HCID 444516386-bromo-2-(3-methoxycarbonylbenzyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic Acid Methyl EsterYield 39.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-bromo-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic acid methyl ester (1.30 g) in dimethylformamide (20 ml) was added sodium hydride (oil, 216 mg), and the mixture was stirred at room temperature for 20 min. 3-Bromomethylbenzoic acid methyl ester (990 mg) was added and the mixture was stirred at room temperature for 5 hrs. The solvent was evaporated under reduced pressure and 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 purified by silica gel column chromatography (n-hexane/ethyl acetate=19/1→4/1) to give the title compound (719 mg, 39%).

Workup

  1. stirringthe mixture was stirred at room temperature for 5 hrs
  2. customThe solvent was evaporated under reduced pressure and 1N hydrochloric acid
  3. additionwas added
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe extract was washed with saturated brine
  6. customdried
  7. additionby adding sodium sulfate
  8. customThe solvent was evaporated under reduced pressure
  9. customthe obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=19/1→4/1)

Sources & evidence

ORD record
ord-5921542135014c079c5775ac13bf96ef
Source dataset
uspto-grants-2008_07
Patent number
US07402595B2

Reaction notes

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