Cesium fluoride → 3-(4'-Chloro-4-ethylbiphen-3-yl)bicyclo[3.2.2]nonane-2,4-dione

HRID 72304Notes

Reaction equation

HRID 72304 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](C)(C)[C:10]([CH3:19])([CH2:11][CH2:12]3)[C:9]2=[O:20])[CH:7]=1.[Cl:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1.[F-].[Cs+]>C(COC)OC.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]>[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([C:2]2[CH:3]=[CH:4][C:5]([CH2:21][CH3:22])=[C:6]([CH:8]3[C:14](=[O:15])[CH:13]4[CH2:16][CH2:19][CH:10]([CH2:11][CH2:12]4)[C:9]3=[O:20])[CH:7]=2)=[CH:26][CH:25]=1

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 742994-Chlorophenylboronic acidHCID 666796443-(5-Bromo-2-ethylphenyl)-1,8,8-trimethylbicyclo[3.2.1]octane-2,4-dione

Product 1

HCID 907057503-(4'-Chloro-4-ethylbiphen-3-yl)bicyclo[3.2.2]nonane-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

A solution of 3-(5-bromo-2-ethyl-phenyl)-1,8,8-trimethylbicyclo[3.2.1]octane-2,4-dione (0.035 g, 0.1 mmol) and 4-chlorophenylboronic acid (0.022 g, 0.14 mmol) in anhydrous dimethoxyethane (2 ml) is stirred at room temperature under an atmosphere of nitrogen. The reaction mixture is then evacuated and flushed with nitrogen (degassing cycle repeated 4 times). Cesium fluoride (0.046 g, 0.30 mmol) is added, and the suspension is stirred at room temperature for 1 hour. Next [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.012 g, 0.015 mmol) is added in one portion, and the reaction mixture is heated at 80° C. for 5.5 hours. After cooling to room temperature the suspension is filtered through diatomaceous earth, then washed with 2M hydrochloric acid (5 ml) and dichloromethane (5 ml). The organic phase is separated, and the aqueous phase is extracted with dichloromethane (5 ml×2). All organics are combined, dried over magnesium sulfate, filtered and the filtrate concentrated under reduced pressure to give a brown gum. The crude product is purified by flash column chromatography on silica gel (100% to 40% hexane/ethyl acetate eluant ratio), then further purified by preparative reverse-phase HPLC to afford to afford 3-(4′-chloro-4-ethylbiphen-3-yl)bicyclo[3.2.2]nonane-2,4-dione.

Workup

  1. customThe reaction mixture is then evacuated
  2. customflushed with nitrogen (degassing cycle repeated 4 times)
  3. temperaturethe reaction mixture is heated at 80° C. for 5.5 hours
  4. temperatureAfter cooling to room temperature the suspension
  5. filtrationis filtered through diatomaceous earth
  6. washwashed with 2M hydrochloric acid (5 ml) and dichloromethane (5 ml)
  7. customThe organic phase is separated
  8. extractionthe aqueous phase is extracted with dichloromethane (5 ml×2)
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationthe filtrate concentrated under reduced pressure
  12. customto give a brown gum
  13. customThe crude product is purified by flash column chromatography on silica gel (100% to 40% hexane/ethyl acetate eluant ratio)
  14. customfurther purified by preparative reverse-phase HPLC
  15. customto afford

Sources & evidence

ORD record
ord-8efe750f57264ee2a79384992bc2b232
Source dataset
uspto-grants-2014_09
Patent number
US08828908B2

Reaction notes

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