N-methyl-2-pyrrolidone → 2-benzyl-6-cyano-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic Acid Methyl Ester

HRID 750163

Reaction equation

HRID 750163 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[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].[CH3:30][N:31]1CCCC1=O>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH3:1][O:2][C:3]([C:5]1[N:6]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[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:30]#[N:31])=[CH:10][CH:9]=2)=[O:4]

Participants

6

Reactant 2

HCID 13387N-methyl-2-pyrrolidoneHCID 444516902-benzyl-6-bromo-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic Acid Methyl Ester

Product 1

HCID 691569922-benzyl-6-cyano-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic Acid Methyl Ester

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-benzyl-6-bromo-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic acid methyl ester (300 mg), zinc cyanide (50 mg), tetrakis(triphenylphosphine)palladium(0) (35 mg) and 1-methyl-2-pyrrolidone (6 ml) was stirred at 100° C. under an argon atmosphere for 2 hrs. Water was added to the reaction mixture, and the mixture was extracted with a mixture of ethyl acetate and THF. The organic layer was washed with aqueous ammonia, water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate) and recrystallized (ethyl acetate-hexane) to give the title compound (230 mg).

Workup

  1. extractionthe mixture was extracted with a mixture of ethyl acetate and THF
  2. washThe organic layer was washed with aqueous ammonia, water and saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate)
  6. customrecrystallized (ethyl acetate-hexane)

Sources & evidence

ORD record
ord-966237eaf8f34faf985501b787ab4511
Source dataset
uspto-grants-2008_07
Patent number
US07402595B2

Linked notes

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