Methanesulfonic Acid → 6-Hydroxy-2-isobutyl-4-(3-methylphenyl)quinoline-3-carbonitrile

HRID 1986451노트

반응식

HRID 1986451 반응식
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][Si](C(C)(C)C)(C)C)=[CH:4][C:3]=1[C:16]([C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH3:24])[CH:19]=1)=O.[CH3:25][CH:26]([CH3:33])[CH2:27][C:28](=O)[CH2:29][C:30]#[N:31].CS(O)(=O)=O>C1(C)C=CC=CC=1>[OH:8][C:5]1[CH:4]=[C:3]2[C:2](=[CH:7][CH:6]=1)[N:1]=[C:28]([CH2:27][CH:26]([CH3:33])[CH3:25])[C:29]([C:30]#[N:31])=[C:16]2[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH3:24])[CH:19]=1

참가 물질

5

반응물 3

HCID 6395Methanesulfonic AcidHCID 30322235-Methyl-3-oxohexanenitrileHCID 68830331(2-Amino-5-{[tert-butyl(dimethyl)silyl]oxy}phenyl)(3-methylphenyl)methanone

생성물 1

HCID 688295476-Hydroxy-2-isobutyl-4-(3-methylphenyl)quinoline-3-carbonitrile수율 56.3%

시약·촉매·용매 1

HCID 1140Toluene용매

실험 절차

To a solution of 2-amino-5-{[tert-butyl(dimethyl)silyl]oxy}-N-methoxy-N-methylbenzamide (2.0 g, 6.4 mmol) in diethyl ether (50 ml) was added dropwise 1.0 M solution of m-tolylmagnesium bromide in tetrahydrofuran (30 ml, 30 mmol) under ice-cooling over 30 min. Ice water (250 g) was added to the reaction mixture and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give (2-amino-5-{[tert-butyl(dimethyl)silyl]oxy}phenyl)(3-methylphenyl)methanone as a mixture. To a solution of the obtained mixture (1.4 g) of (2-amino-5-{[tert-butyl(dimethyl)silyl]oxy}phenyl)(3-methylphenyl)methanone and 5-methyl-3-oxohexanenitrile (0.60 g, 4.7 mmol) in toluene (50 ml) was added methanesulfonic acid (0.38 g, 4.0 mmol), and the mixture was heated under reflux for 6 hrs. The reaction mixture was partitioned between ethyl acetate (100 ml) and saturated aqueous sodium hydrogen carbonate (100 ml), and the organic layer was washed with saturated brine (50 ml) and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained crude crystals were recrystallized from n-hexane-ethyl acetate to give 6-hydroxy-2-isobutyl-4-(3-methylphenyl)quinoline-3-carbonitrile (0.73 g, yield 36%) as pale-yellow crystals.

후처리

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 6 hrs
  3. customThe reaction mixture was partitioned between ethyl acetate (100 ml) and saturated aqueous sodium hydrogen carbonate (100 ml)
  4. washthe organic layer was washed with saturated brine (50 ml)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customthe obtained crude crystals
  8. customwere recrystallized from n-hexane-ethyl acetate

출처 및 근거

ORD 기록
ord-0d7f2f790476456c9a82500fa8d9bd9c
출처 데이터셋
uspto-grants-2009_06
특허 번호
US07547710B2

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