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 525882ノート

反応式

HRID 525882 の反応式
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

参加物

7

反応物 2

HCID 867327488-bromo-3-((4-methoxybenzyl)oxy)-1-methylquinolin-4(1H)-oneHCID 178514179HCID 178514179、化合物

生成物 1

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

試薬・触媒・溶媒 4

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 178418397HCID 178418397、化合物触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
110 °C

実験手順

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.

後処理

  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%)

出典と根拠

ORDレコード
ord-6ff1bdb4c54b4f26ab7f36404279347b
出典データセット
uspto-grants-2016_05
特許番号
US09340556B2

反応ノート

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