8-Hydroxyquinoline → 3-(4-bromophenyl)-1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazole

HRID 62061

Reaction equation

HRID 62061 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[CH:11][NH:10][N:9]=2)=[CH:4][CH:3]=1.I[C:14]1[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=1.OC1C=CC=C2C=1N=CC=C2.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.O.C(OCC)(=O)C.[Cu]I>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:12]=[CH:11][N:10]([C:14]3[CH:15]=[CH:16][C:17]([O:20][C:21]([F:22])([F:23])[F:24])=[CH:18][CH:19]=3)[N:9]=2)=[CH:6][CH:7]=1

Participants

9

Reactant 4

HCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 27772941-Iodo-4-(trifluoromethoxy)benzeneHCID 469487345-(4-Bromophenyl)-1H-1,2,4-triazole

Product 1

HCID 904040773-(4-bromophenyl)-1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazoleYield 29.1%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

In a 500 mL flask, 3-(4-bromophenyl)-1H-1,2,4-triazole (20.0 g, 89.6 mmol), 1-iodo-4-(trifluoromethoxy)benzene (39.0 g, 135 mmol) were diluted with N,N-dimethylformamide and water (4:1, 100 mL). Then copper(I) iodide (15.3 g, 80.6 mmol), 8-hydroxyquinoline (8.50 g, 58.2 mmol) and cesium carbonate (87.4 g, 269 mmol) were added. The reaction was heated to 150° C. and stirred for 16 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate and filtered through Celite®. Brine solution was added to the filtrate and stirred for 15 minutes. The layers were separated and the aqueous layer further extracted with ethyl acetate. The combined organics were dried over magnesium sulfate, filtered, and concentrated. The resulting residue was purified by flash column chromatography using 15% ethyl acetate/petroleum ether as eluent to afford the title compound as a white solid (10.0 g, 29%): mp 100-103° C.; 1H NMR (300 MHz, DMSO-d6) δ 9.42 (s, 1H), 8.07 (d, J=9.0 Hz, 2H), 8.05 (d, J=9.0 Hz, 2H), 7.73 (d, J=8.4 Hz, 2H), 7.62 (d, J=8.4 Hz, 2H); ES+ m/z 385 ([M+H]+).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered through Celite®
  3. additionBrine solution was added to the filtrate
  4. stirringstirred for 15 minutes
  5. customThe layers were separated
  6. extractionthe aqueous layer further extracted with ethyl acetate
  7. dry with materialThe combined organics were dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-8625bc0c58914aa885a3863b65ef9362
Source dataset
uspto-grants-2016_09
Patent number
US09445594B2

Linked notes

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