2,4-Dichlorophenol → rac-(1S,5R)-3-[5-(2,4-dichlorophenoxy)-2-ethylphenyl]-1,8,8-trimethylbicyclo[3.2.1]octane-2,4-dione

HRID 537676Notes

Reaction equation

HRID 537676 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:21][CH3:22])=[C:6]([CH:8]2[C:14](=[O:15])[CH:13]3[C:16]([CH3:18])([CH3:17])[C:10]([CH3:19])([CH2:11][CH2:12]3)[C:9]2=[O:20])[CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[Cl:29][C:30]1[CH:35]=[C:34]([Cl:36])[CH:33]=[CH:32][C:31]=1[OH:37]>FC(F)(F)S([O-])(=O)=O.[Cu+2].FC(F)(F)S([O-])(=O)=O.C1(C)C=CC=CC=1>[Cl:29][C:30]1[CH:35]=[C:34]([Cl:36])[CH:33]=[CH:32][C:31]=1[O:37][C:2]1[CH:3]=[CH:4][C:5]([CH2:21][CH3:22])=[C:6]([CH:8]2[C:14](=[O:15])[CH:13]3[C:16]([CH3:18])([CH3:17])[C:10]([CH3:19])([CH2:11][CH2:12]3)[C:9]2=[O:20])[CH:7]=1

Participants

6

Reactant 3

HCID 84492,4-DichlorophenolHCID 10796Cesium carbonateHCID 666796443-(5-Bromo-2-ethylphenyl)-1,8,8-trimethylbicyclo[3.2.1]octane-2,4-dione

Product 1

HCID 66680478rac-(1S,5R)-3-[5-(2,4-dichlorophenoxy)-2-ethylphenyl]-1,8,8-trimethylbicyclo[3.2.1]octane-2,4-dione

Reagents, catalysts & solvents 2

HCID 2734996copper(II) trifluoromethanesulfonateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
170 °C

Procedure

To a mixture of rac-3-(5-bromo-2-ethylphenyl)-1,8,8-trimethylbicyclo[3.2.1]octane-2,4-dione (0.175 g, 0.48 mmol), cesium carbonate (0.314 g, 0.96 mmol) and 2,4-dichlorophenol (0.393 g, 2.41 mmol) is added copper (II) trifluoromethanesulfonate (0.009 g, 0.024 mmol) and powdered 3 Å molecular sieves (0.200 g). Degassed anhydrous toluene (2 ml) is then added, followed by purging with nitrogen and heating at 170° C. for 1 hour under microwave irradiation. After cooling to room temperature the reaction mixture is quenched with 2M aqueous hydrochloric acid and extracted with dichloromethane (×2). The organic phase is separated and concentrated under reduced pressure. The crude product is then purified by preparative reverse phase HPLC to afford rac-(1S,5R)-3-[5-(2,4-dichlorophenoxy)-2-ethylphenyl]-1,8,8-trimethylbicyclo[3.2.1]octane-2,4-dione.

Workup

  1. customby purging with nitrogen
  2. temperatureAfter cooling to room temperature the reaction mixture
  3. customis quenched with 2M aqueous hydrochloric acid
  4. extractionextracted with dichloromethane (×2)
  5. customThe organic phase is separated
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product is then purified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-bc95a3534d304af7b9f4922945a75cf4
Source dataset
uspto-grants-2014_10
Patent number
US08865623B2

Reaction notes

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