Cesium carbonate → 4-[4-(4-Chloro-3-fluorophenoxy)-2-ethylphenyl]-2,2,6,6-tetramethylpyran-3,5-dione

HRID 512578Notes

Reaction equation

HRID 512578 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([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])=[C:4]([CH2:20][CH3:21])[CH:3]=1.[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][C:24]=1[F:30].C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.ClCCl.Cl.FC(F)(F)S([O-])(=O)=O.[Cu+2].FC(F)(F)S([O-])(=O)=O>[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][C:2]2[CH:7]=[CH:6][C:5]([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])=[C:4]([CH2:20][CH3:21])[CH:3]=2)=[CH:25][C:24]=1[F:30]

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 27245234-Chloro-3-fluorophenolHCID 497653874-(4-Bromo-2-ethylphenyl)-2,2,6,6-tetramethylpyran-3,5-dione

Product 1

HCID 666777344-[4-(4-Chloro-3-fluorophenoxy)-2-ethylphenyl]-2,2,6,6-tetramethylpyran-3,5-dione

Reagents, catalysts & solvents 4

HCID 2734996copper(II) trifluoromethanesulfonateCatalystHCID 313Hydrochloric AcidSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of 4-(4-bromo-2-ethylphenyl)-2,2,6,6-tetramethylpyran-3,5-dione (0.20 g, 0.57 mmol), 4-chloro-3-fluorophenol (0.41 g, 2.83 mmol), cesium carbonate (0.40 g, 1.13 mmol), copper(II) trifluoromethanesulfonate (0.01 g, 0.03 mmol) and powdered molecular sieve, 4 Å (0.40 g) in dry toluene (3.5 ml) is heated to 160° C. under microwave irradiation for 1 hour. The mixture is cooled to room temperature diluted with dichloromethane and 2M aqueous hydrochloric acid (10 ml) and passed through a phase separation cartridge. The organic phase is dried over anhydrous magnesium sulfate, filtered and the filtrate is evaporated under reduced pressure. The residue is dissolved in N,N-dimethylformamide (1 ml) and purified by preparative reverse phase HPLC to give 4-[4-(4-chloro-3-fluorophenoxy)-2-ethylphenyl]-2,2,6,6-tetramethylpyran-3,5-dione.

Workup

  1. temperatureThe mixture is cooled to room temperature
  2. custompassed through a phase separation cartridge
  3. dry with materialThe organic phase is dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customthe filtrate is evaporated under reduced pressure
  6. dissolutionThe residue is dissolved in N,N-dimethylformamide (1 ml)
  7. custompurified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-570eafc324334c1e89548e3de89fb7da
Source dataset
uspto-grants-2015_08
Patent number
US09102642B2

Reaction notes

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