Hydrochloric Acid → 1-(4-pentafluoroethyloxy-phenyl)-3-p-tolyl-1H-[1,2,4]triazole

HRID 1192795Notes

Reaction equation

HRID 1192795 reaction equation
[C:1]1([CH3:12])[CH:6]=[CH:5][C:4]([C:7]2[N:11]=[CH:10][NH:9][N:8]=2)=[CH:3][CH:2]=1.[F:13][C:14]([O:20][C:21]1[CH:26]=[CH:25][C:24](Br)=[CH:23][CH:22]=1)([F:19])[C:15]([F:18])([F:17])[F:16].C([O-])([O-])=O.[Cs+].[Cs+].OC1C=CC=C2C=1N=CC=C2.Cl>[Cu]I.CCOCC.O.CN(C=O)C.O>[F:13][C:14]([F:19])([O:20][C:21]1[CH:22]=[CH:23][C:24]([N:9]2[CH:10]=[N:11][C:7]([C:4]3[CH:3]=[CH:2][C:1]([CH3:12])=[CH:6][CH:5]=3)=[N:8]2)=[CH:25][CH:26]=1)[C:15]([F:16])([F:18])[F:17]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 918531-Bromo-4-(pentafluoroethoxy)benzeneHCID 178423994HCID 178423994, compound

Product 1

HCID 866333811-(4-pentafluoroethyloxy-phenyl)-3-p-tolyl-1H-[1,2,4]triazoleYield 62.1%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Conditions

Temperature
130 °C

Procedure

A solution of 3-p-tolyl-1H-[1,2,4]triazole (4.85 g, 30.5 mmol), 4-bromophenyl pentafluoroethyl ether (10.0 g, 34.4 mmol), Cs2CO3 (25 g, 77 mmol), CuI (1.25 g, 6.5 mmol) and 8-hydroxyquinoline (0.35 g, 2.4 mmol) in 9:1 DMF/H2O (50 mL) was stirred vigorously and heated to 130° C. (internal temperature) for 20 h. The solution was then cooled, poured into H2O, and acidified with 2 N HCl to pH 2. Ether (250 mL) was then added and the solution was shaken and filtered before separating layers. The organic layer was dried and concentrated, and the resulting gummy solid was heated with hexanes (100 mL). The hot hexane layer was decanted from insoluble residue, the resulting solution cooled to 0° C. and the precipitated solid was filtered and air-dried to furnish 1-(4-pentafluoroethyloxy-phenyl)-3-p-tolyl-1H-[1,2,4]triazole (7.0 g, 61% based on starting triazole) as an off-white solid: mp 130-132° C.; ESIMS m/z 370.8 (M+H).

Workup

  1. temperatureThe solution was then cooled
  2. filtrationfiltered
  3. custombefore separating layers
  4. customThe organic layer was dried
  5. concentrationconcentrated
  6. temperaturethe resulting gummy solid was heated with hexanes (100 mL)
  7. customThe hot hexane layer was decanted from insoluble residue
  8. temperaturethe resulting solution cooled to 0° C.
  9. filtrationthe precipitated solid was filtered
  10. customair-dried

Sources & evidence

ORD record
ord-4032aecface0405da07685a3401a1bb2
Source dataset
uspto-grants-2014_03
Patent number
US08680269B2

Reaction notes

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