Cesium fluoride → 3-(2',4'-Dichloro-4-ethylbiphen-3-yl)bicyclo[3.2.1]octane-2,4-dione

HRID 72263Notes

Reaction equation

HRID 72263 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:18][CH3:19])=[C:6]([CH:8]2[C:14](=[O:15])[CH:13]3[CH2:16][CH:10]([CH2:11][CH2:12]3)[C:9]2=[O:17])[CH:7]=1.[Cl:20][C:21]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:22]=1B(O)O.[F-].[Cs+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(COC)OC>[Cl:20][C:21]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:22]=1[C:2]1[CH:3]=[CH:4][C:5]([CH2:18][CH3:19])=[C:6]([CH:8]2[C:14](=[O:15])[CH:13]3[CH2:16][CH:10]([CH2:11][CH2:12]3)[C:9]2=[O:17])[CH:7]=1

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 2734659(2,4-Dichlorophenyl)boronic acidHCID 666795693-(5-Bromo-2-ethylphenyl)bicyclo[3.2.1]octane-2,4-dione

Product 1

HCID 912810483-(2',4'-Dichloro-4-ethylbiphen-3-yl)bicyclo[3.2.1]octane-2,4-dione

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a microwave vial is added 3-(5-bromo-2-ethylphenyl)bicyclo[3.2.1]octane-2,4-dione (0.200 g, 0.623 mmol), 2,4-dichlorophenyl boronic acid (0.167 g, 0.87 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.040 g, 0.05 mmol) and cesium fluoride (0.284 g, 1.87 mmol). Degassed dimethoxyethane is next added (washing down any solids from the slides of the vial), followed by purging with nitrogen then stirring at room temperature for 5 minutes. The mixture is heated at 160° C. under microwave irradiation for 15 minutes, cooled to room temperature, then partitioned between 2M hydrochloric acid and dichloromethane. After separation of the organic layer the aqueous phase is again washed with dichloromethane, then all organic fractions are combined and concentrated in vacuo to afford a crude gum. This crude product is purified by flash column chromatography on silica gel (30% to 100% ethyl acetate/iso-hexane eluant ratio) to afford 3-(2′,4′-dichloro-4-ethylbiphen-3-yl)bicyclo[3.2.1]octane-2,4-dione.

Workup

  1. washwashing down any solids from the slides of the vial),
  2. customby purging with nitrogen
  3. temperatureThe mixture is heated at 160° C. under microwave irradiation for 15 minutes
  4. temperaturecooled to room temperature
  5. custompartitioned between 2M hydrochloric acid and dichloromethane
  6. customAfter separation of the organic layer the aqueous phase
  7. washis again washed with dichloromethane
  8. concentrationconcentrated in vacuo
  9. customto afford a crude gum
  10. customThis crude product is purified by flash column chromatography on silica gel (30% to 100% ethyl acetate/iso-hexane eluant ratio)

Sources & evidence

ORD record
ord-579c355a27aa4369a07860df6401e411
Source dataset
uspto-grants-2014_09
Patent number
US08828908B2

Reaction notes

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