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

HRID 1925411Notes

Reaction equation

HRID 1925411 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>CN(C=O)C.O.[Cu]I.CCOCC.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 50 mL of 9:1 DMF/H2O was stirred vigorously and heated to 130° C. (internal temperature) for 20 h. The solution was then cooled, poured into water, 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 100 mL of hexanes. 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 7.0 g (61% based on starting triazole) of 1-(4-pentafluoroethyloxy-phenyl)-3-p-tolyl-1H-[1,2,4]triazole as an off-white solid, mp 130-132° C.; ESIMS 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 100 mL of hexanes
  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-3249296f249041a28d79f0895049076c
Source dataset
uspto-grants-2012_05
Patent number
US08178658B2

Reaction notes

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