Methanol → 2-(4-tert-butoxycarbonylbenzyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3,6-dicarboxylic Acid Dimethyl Ester

HRID 750253Notes

Reaction equation

HRID 750253 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[CH:26][CH:25]=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)=[CH:10][CH:9]=2)=[O:4].C(N(CC)CC)C.CN([CH:47]=[O:48])C.[C]=O.[CH3:51][OH:52]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH3:1][O:2][C:3]([C:5]1[N:6]([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[CH:26][CH:25]=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]([C:51]([O:48][CH3:47])=[O:52])=[CH:10][CH:9]=2)=[O:4]

Participants

8

Reactant 5

HCID 887MethanolHCID 6228DimethylformamideHCID 8471TriethylamineHCID 691566226-bromo-2-(4-tert-butoxycarbonylbenzyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic Acid Methyl EsterHCID 178418416HCID 178418416, compound

Product 1

HCID 691568282-(4-tert-butoxycarbonylbenzyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3,6-dicarboxylic Acid Dimethyl Ester

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst

Conditions

Temperature
60 °C

Procedure

A mixture of 6-bromo-2-(4-tert-butoxycarbonylbenzyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic acid methyl ester (2.54 g), palladium(II) acetate (52 mg), 1,1′-bis(diphenylphosphino)ferrocene (125 mg), triethylamine (1.6 ml), DMF (13 ml) and methanol (13 ml) was stirred at 60° C. for 72 hrs. under 1 atm carbon monoxide. The reaction mixture was concentrated and water was added to the residue. The mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane-hexane:ethyl acetate=2:1) and recrystallized (ethyl acetate-hexane) to give the title compound (1.82 g).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionwater was added to the residue
  3. extractionThe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with water and saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (hexane-hexane:ethyl acetate=2:1)
  8. customrecrystallized (ethyl acetate-hexane)

Sources & evidence

ORD record
ord-a9e462e94aba45bbbefc5f078fa4d604
Source dataset
uspto-grants-2008_07
Patent number
US07402595B2

Reaction notes

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