8-Hydroxyquinoline → 4-(1-(4-(Trifluoromethoxy)phenyl)-1H-pyrazol-3-yl)benzoic acid

HRID 59868

反応式

HRID 59868 の反応式
[NH:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:15]=[CH:14][C:9]([C:10]([O:12]C)=[O:11])=[CH:8][CH:7]=2)=[N:2]1.Br[C:17]1[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=1.OC1C=CC=C2C=1N=CC=C2.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O.O.CCOC(C)=O.[Cu]I>[F:25][C:24]([F:26])([F:27])[O:23][C:20]1[CH:21]=[CH:22][C:17]([N:1]2[CH:5]=[CH:4][C:3]([C:6]3[CH:15]=[CH:14][C:9]([C:10]([OH:12])=[O:11])=[CH:8][CH:7]=3)=[N:2]2)=[CH:18][CH:19]=1

参加物

9

反応物 4

HCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 5210081-Bromo-4-(trifluoromethoxy)benzeneHCID 178497540Methyl 4-(1H-pyrazol-5-yl)benzoate

生成物 1

HCID 581567244-(1-(4-(Trifluoromethoxy)phenyl)-1H-pyrazol-3-yl)benzoic acid収率 16.9%

試薬・触媒・溶媒 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 21962138N,N-Dimethylformamide--water (1/1)溶媒

実験手順

Methyl 4-(1H-pyrazol-3-yl)benzoate (2.00 g, 9.89 mmol), 1-bromo-4-(trifluoromethoxy)benzene (2.38 g, 9.88 mmol), copper (I) iodide (0.28 g, 1.47 mmol), 8-hydroxyquinoline (0.21 g, 1.45 mmol), and cesium carbonate (6.47 g, 19.86 mmol) in DMF/water (11:1) was heated at 120° C. for 20 hours. The reaction was cooled, diluted with water and EtOAc, and decanted from the copper solids. The mixture was extracted three times with EtOAc (3×150 mL) and the combined organic layers washed with water. The organic layers were dried over anhydrous sodium sulfate, filtered, and adsorbed onto silica gel. Purification by flash chromatography (0-10% MeOH/dichloromethane) gave 4-(1-(4-(trifluoromethoxy)phenyl)-1H-pyrazol-3-yl)benzoic acid as a brown solid (580 mg, 16%): 1H NMR (400 MHz, CDCl3) δ 8.19 (d, J=7.7 Hz, 2H), 8.03 (d, J=7.7 Hz, 2H), 7.98 (d, J=2.5 Hz, 1H), 7.85-7.79 (m, 2H), 7.35 (d, J=8.4 Hz, 2H), 6.88 (d, J=2.5 Hz, 1H); 19F NMR (376 MHz, CDCl3) δ −58.05; ESIMS m/z 349 ([M+H]+).

後処理

  1. temperatureThe reaction was cooled
  2. customdecanted from the copper solids
  3. extractionThe mixture was extracted three times with EtOAc (3×150 mL)
  4. washthe combined organic layers washed with water
  5. dry with materialThe organic layers were dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customPurification by flash chromatography (0-10% MeOH/dichloromethane)

出典と根拠

ORDレコード
ord-eb898592236442ff8a79b991420b575a
出典データセット
uspto-grants-2016_09
特許番号
US09440964B2

関連ノート

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