Hydrochloric Acid → 3-(5-Bromo-2-ethylphenyl)-bicyclo[3.2.2]nonane-2,4-dione

HRID 72273Notes

Reaction equation

HRID 72273 reaction equation
[CH:1]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[C:4](=[O:10])[CH2:3][C:2]2=[O:11].C1(C)C=CC=CC=1.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Br:31][C:32]1[CH:33]=[CH:34][C:35]([CH2:39][CH3:40])=[C:36]([Pb+3])[CH:37]=1.Cl>C(Cl)(Cl)Cl.CN(C)C1C=CN=CC=1.ClCCl>[Br:31][C:32]1[CH:37]=[CH:36][C:35]([CH2:39][CH3:40])=[C:34]([CH:3]2[C:2](=[O:11])[CH:1]3[CH2:7][CH2:6][CH:5]([CH2:8][CH2:9]3)[C:4]2=[O:10])[CH:33]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 1140TolueneHCID 144687Bicyclo[3.2.2]nonane-2,4-dioneHCID 178476533HCID 178476533, compound

Product 1

HCID 684855023-(5-Bromo-2-ethylphenyl)-bicyclo[3.2.2]nonane-2,4-dioneYield 49.1%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of bicyclo[3.2.2]nonane-2,4-dione (0.12 g, 0.79 mmol), prepared by the method of W. Childers et al., US2006/0004108, in dry chloroform (4 ml) is stirred at room temperature then thoroughly flushed with nitrogen. To this mixture is then added 4-dimethylaminopyridine (0.482 g, 3.95 mmol) and anhydrous toluene (1 ml), followed by heating to 80° C. 5-Bromo-2-ethylphenyllead triacetate (0.673 g, 1.18 mmol) is added in one portion, and the mixture is further heated at this temperature for a further 4 hours then left to stand overnight. Dichloromethane (10 ml) and 2M hydrochloric acid (10 ml) are added, and the resulting biphasic mixture is filtered to remove any inorganic salts (washing with additional dichloromethane, 10 ml). The organic phase separated, and the aqueous phase is extracted again with dichloromethane (10 ml×2). All organic fractions are combined, dried over magnesium sulfate, filtered and the filtrate concentrated under reduced pressure to give a yellow gum. This crude product is purified by flash column chromatography on silica gel (100% to 40% hexane/ethyl acetate eluant ratio) to afford 3-(5-bromo-2-ethylphenyl)-bicyclo[3.2.2]nonane-2,4-dione (0.130 g, 49%) as a yellow solid.

Workup

  1. customthen thoroughly flushed with nitrogen
  2. temperaturethe mixture is further heated at this temperature for a further 4 hours
  3. waitthen left
  4. filtrationthe resulting biphasic mixture is filtered
  5. customto remove
  6. washany inorganic salts (washing with additional dichloromethane, 10 ml)
  7. customThe organic phase separated
  8. extractionthe aqueous phase is extracted again with dichloromethane (10 ml×2)
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationthe filtrate concentrated under reduced pressure
  12. customto give a yellow gum
  13. customThis crude product is purified by flash column chromatography on silica gel (100% to 40% hexane/ethyl acetate eluant ratio)

Sources & evidence

ORD record
ord-85ab4a4823e64ac184274d5a2601fc0c
Source dataset
uspto-grants-2014_09
Patent number
US08828908B2

Reaction notes

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