Hydrochloric Acid → 3-(5-Bromo-2-ethylphenyl)bicyclo[3.2.2]non-6-ene-2,4-dione

HRID 72275Notes

Reaction equation

HRID 72275 reaction equation
[CH:1]12[CH2:9][CH2:8][CH:5]([CH:6]=[CH: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>[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[CH2:9][CH2:8][CH:5]([CH:6]=[CH:7]3)[C:4]2=[O:10])[CH:33]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 1140TolueneHCID 58609528HCID 58609528, compoundHCID 178476533HCID 178476533, compound

Product 1

HCID 684883343-(5-Bromo-2-ethylphenyl)bicyclo[3.2.2]non-6-ene-2,4-dioneYield 22%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6212ChloroformSolvent

Conditions

Temperature
80 °C

Procedure

A solution of bicyclo[3.2.2]non-6-ene-2,4-dione (0.835 g, 5.58 mmol), prepared by the method of R. Beaudegnies et al., WO2005/123667, in dry chloroform (30 ml) is stirred at room temperature then thoroughly flushed with nitrogen. To this mixture is added 4-dimethylaminopyridine (3.41 g, 28 mmol) and anhydrous toluene (5 ml), followed by heating to 80° C. 5-Bromo-2-ethylphenyllead triacetate (4.75 g, 8.36 mmol) is added portionwise over 20 minutes, and the mixture is further heated at this temperature for a further 4 hours then left to stand overnight. 2M hydrochloric acid (40 ml) is added, and the suspension is vigorously stirred for 30 minutes then filtered through diatomaceous earth (washing with additional dichloromethane, 40 ml). The organic phase is separated, and the aqueous phase is extracted with dichloromethane (40 ml×2). All organic fractions are combined, dried over magnesium sulfate, filtered and the filtrate concentrated under reduced pressure to give a brown oil. The 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]non-6-ene-2,4-dione (0.400 g, 22%) as a yellow gum.

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. filtrationthen filtered through diatomaceous earth (washing with additional dichloromethane, 40 ml)
  5. customThe organic phase is separated
  6. extractionthe aqueous phase is extracted with dichloromethane (40 ml×2)
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationthe filtrate concentrated under reduced pressure
  10. customto give a brown oil
  11. customThe crude product is purified by flash column chromatography on silica gel (100% to 40% hexane/ethyl acetate eluant ratio)

Sources & evidence

ORD record
ord-e2d6cd26354c46c3a7c901e8ade2a19f
Source dataset
uspto-grants-2014_09
Patent number
US08828908B2

Reaction notes

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