4-Chlorophenol → 2-[5-(4-Chlorophenoxy)-2-cyclopropylphenyl]cyclopentane-1,3-dione

HRID 339477Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]([CH:15]2[CH2:17][CH2:16]2)=[C:6]([CH:8]2[C:12](=[O:13])[CH2:11][CH2:10][C:9]2=[O:14])[CH:7]=1.[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=1.[F-].[Cs+]>[O-]S(C(F)(F)F)(=O)=O.[Cu+2].[O-]S(C(F)(F)F)(=O)=O.C1(C)C=CC=CC=1>[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][C:2]2[CH:3]=[CH:4][C:5]([CH:15]3[CH2:17][CH2:16]3)=[C:6]([CH:8]3[C:12](=[O:13])[CH2:11][CH2:10][C:9]3=[O:14])[CH:7]=2)=[CH:21][CH:20]=1

Participants

Conditions

Temperature: 160 °C

Procedure

To a mixture of 2-(5-bromo-2-cyclopropylphenyl)cyclopentane-1,3-dione (0.254 g, 0.062 mmol), 4-chlorophenol (0.400 g, 3.11 mmol), cesium fluoride (0.440 g, 1.25 mmol) and copper (II) triflate (11 mg, 0.03 mmol) is added 4 Å powdered molecular sieves (0.40 g) and anhydrous toluene (3.5 ml). This mixture is then heated at 160° C. for 1 hour under microwave irradiation, allowed to cool to room temperature then quenched with 2M hydrochloric acid. The reaction mixture is extracted with dichloromethane (×3), then the combined organics are washed with brine, dried over magnesium sulfate and concentrated in vacuo. The crude product is purified by preparative reverse phase HPLC to afford 2-[5-(4-chlorophenoxy)-2-cyclopropylphenyl]cyclopentane-1,3-dione as a white solid.

Workup

additionis added 4 Å
temperatureto cool to room temperature
customthen quenched with 2M hydrochloric acid
extractionThe reaction mixture is extracted with dichloromethane (×3)
washthe combined organics are washed with brine
dry with materialdried over magnesium sulfate
concentrationconcentrated in vacuo
customThe crude product is purified by preparative reverse phase HPLC

Sources & evidence

ORD record: ord-a3f540010ee74de4b1b58ede3f328a80
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08895474B2

Reaction notes

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