4-Chlorophenol → 4-[5-(4-Chloro-phenoxy)-2-trifluoromethoxyphenyl]-2,2,6,6-tetramethylpyran-3,5-dione

HRID 537692Notes

Reaction equation

HRID 537692 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:20][C:21]([F:24])([F:23])[F:22])=[C:6]([CH:8]2[C:13](=[O:14])[C:12]([CH3:16])([CH3:15])[O:11][C:10]([CH3:18])([CH3:17])[C:9]2=[O:19])[CH:7]=1.[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>FC(F)(F)S([O-])(=O)=O.[Cu+2].FC(F)(F)S([O-])(=O)=O.C1(C)C=CC=CC=1>[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][C:2]2[CH:3]=[CH:4][C:5]([O:20][C:21]([F:24])([F:23])[F:22])=[C:6]([CH:8]3[C:13](=[O:14])[C:12]([CH3:16])([CH3:15])[O:11][C:10]([CH3:18])([CH3:17])[C:9]3=[O:19])[CH:7]=2)=[CH:28][CH:27]=1

Participants

6

Reactant 3

HCID 46844-ChlorophenolHCID 10796Cesium carbonateHCID 666804614-(5-Bromo-2-trifluoromethoxyphenyl)-2,2,6,6-tetramethylpyran-3,5-dione

Product 1

HCID 666785934-[5-(4-Chloro-phenoxy)-2-trifluoromethoxyphenyl]-2,2,6,6-tetramethylpyran-3,5-dione

Reagents, catalysts & solvents 2

HCID 2734996copper(II) trifluoromethanesulfonateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
160 °C

Procedure

To a mixture of 4-(5-bromo-2-trifluoromethoxyphenyl)-2,2,6,6-tetramethylpyran-3,5-dione (0.254 g, 0.62 mmol), 4-chlorophenol (0.400 g, 3.11 mmol), cesium carbonate (0.440 g, 1.25 mmol), copper (II) trifluoromethanesulfonate (11 mg, 0.03 mmol) and powdered 4 Å molecular sieves (0.40 g) is added anhydrous toluene (3.5 ml). After flushing with nitrogen the mixture is heated at 160° C. for 1 hour under microwave irradiation, then cooled to room temperature and quenched with 2M aqueous hydrochloric acid. The crude product is extracted with dichloromethane (×3), and the organic fractions are combined, washed with brine, dried over magnesium sulfate and concentrated in vacuo. Purification by preparative reverse phase HPLC affords 4-[5-(4-chlorophenoxy)-2-trifluoromethoxyphenyl]-2,2,6,6-tetramethylpyran-3,5-dione as a white powder.

Workup

  1. customAfter flushing with nitrogen the mixture
  2. temperaturecooled to room temperature
  3. customquenched with 2M aqueous hydrochloric acid
  4. extractionThe crude product is extracted with dichloromethane (×3)
  5. washwashed with brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customPurification by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-89205fb79b0141a2a67cb9b514a5d5b6
Source dataset
uspto-grants-2014_10
Patent number
US08865623B2

Reaction notes

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