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 525882노트

반응식

HRID 525882 반응식
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

참가 물질

7

반응물 2

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

생성물 1

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

시약·촉매·용매 4

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 178418397HCID 178418397, 화합물촉매HCID 6228Dimethylformamide용매

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온도
110 °C

실험 절차

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.

후처리

  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%)

출처 및 근거

ORD 기록
ord-6ff1bdb4c54b4f26ab7f36404279347b
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09340556B2

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