8-bromo-3-((4-methoxybenzyl)oxy)-1-methylquinolin-4(1H)-one → 3-((4-Methoxybenzyl)oxy)-1-methyl-4-oxo-1,4-dihydroquinolin-8-carbonitrile

HRID 525882Notes

Reaction equation

HRID 525882 reaction equation
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]([CH3:12])[CH:9]=[C:8]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=1)[C:7]2=[O:23].[C:24]([Zn]C#N)#[N:25]>CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:22][O:21][C:18]1[CH:19]=[CH:20][C:15]([CH2:14][O:13][C:8]2[C:7](=[O:23])[C:6]3[C:11](=[C:2]([C:24]#[N:25])[CH:3]=[CH:4][CH:5]=3)[N:10]([CH3:12])[CH:9]=2)=[CH:16][CH:17]=1

Participants

7

Reactant 2

HCID 867327488-bromo-3-((4-methoxybenzyl)oxy)-1-methylquinolin-4(1H)-oneHCID 178514179HCID 178514179, compound

Product 1

HCID 867327493-((4-Methoxybenzyl)oxy)-1-methyl-4-oxo-1,4-dihydroquinolin-8-carbonitrileYield 84%

Reagents, catalysts & solvents 4

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To a suspension of 8-bromo-3-((4-methoxybenzyl)oxy)-1-methylquinolin-4(1H)-one (2.6 g, 6.95 mmol), DPPF (0.462 g, 0.834 mmol), palladium tetrakis (0.482 g, 0.417 mmol) and Pd2(dba)3 (0.382 g, 0.417 mmol) in N,N-dimethylformamide (30 mL) at room temperature was added dicyanozinc (0.979 g, 8.34 mmol). The mixture was then heated at 110° C. under N2 for 1 h. After cooled to room temperature, the mixture was concentrated in vacuo and then partitioned between EtOAc (80 mL) and conc. NH4Cl (40 mL). The organic phase was separated, washed with brine (40 mL), dried over sodium sulfate, and concentrated. The residue was purified twice by automatic silica gel column chromatography (Combiflash RF), eluting with ethyl acetate/hexanes (0-100%) to afford 3-((4-methoxybenzyl)oxy)-1-methyl-4-oxo-1,4-dihydroquinoline-8-carbonitrile (1.87 g, 5.84 mmol, 84% yield) as a light brown solid. LCMS: (M+H)+: 321.1.

Workup

  1. temperatureAfter cooled to room temperature
  2. concentrationthe mixture was concentrated in vacuo
  3. custompartitioned between EtOAc (80 mL) and conc. NH4Cl (40 mL)
  4. customThe organic phase was separated
  5. washwashed with brine (40 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified twice by automatic silica gel column chromatography (Combiflash RF)
  9. washeluting with ethyl acetate/hexanes (0-100%)

Sources & evidence

ORD record
ord-6ff1bdb4c54b4f26ab7f36404279347b
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

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