Hydrochloric Acid → 3-(5-Bromo-2-ethylphenyl)-1,8,8-trimethylbicyclo[3.2.1]octane-2,4-dione

HRID 72303Notes

Reaction equation

HRID 72303 reaction equation
[CH3:1][C:2]12[C:9]([CH3:11])([CH3:10])[CH:6]([CH2:7][CH2:8]1)[C:5](=[O:12])[CH2:4][C:3]2=[O:13].C1(C)C=CC=CC=1.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Br:33][C:34]1[CH:35]=[CH:36][C:37]([CH2:41][CH3:42])=[C:38]([Pb+3])[CH:39]=1.Cl>C(Cl)(Cl)Cl.CN(C)C1C=CN=CC=1>[Br:33][C:34]1[CH:39]=[CH:38][C:37]([CH2:41][CH3:42])=[C:36]([CH:4]2[C:5](=[O:12])[CH:6]3[C:9]([CH3:10])([CH3:11])[C:2]([CH3:1])([CH2:8][CH2:7]3)[C:3]2=[O:13])[CH:35]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 1140TolueneHCID 1378761,8,8-Trimethylbicyclo[3.2.1]octane-2,4-dioneHCID 178476533HCID 178476533, compound

Product 1

HCID 666796443-(5-Bromo-2-ethylphenyl)-1,8,8-trimethylbicyclo[3.2.1]octane-2,4-dioneYield 9.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6212ChloroformSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 1,8,8-trimethylbicyclo[3.2.1]octane-2,4-dione (0.22 g, 1.22 mmol) (preparation described by H. Favre et al., Can. J. Chem. (1956), 34 1329-39) in dry chloroform (10 ml) is stirred at room temperature then thoroughly flushed with nitrogen. To this mixture is then added 4-dimethylaminopyridine (0.744 g, 6.15 mmol) and anhydrous toluene (3 ml), followed by heating to 80° C. 5-Bromo-2-ethylphenyllead triacetate (0.673 g, 1.18 mmol) is added portionwise over 10 minutes, and the mixture is further heated at this temperature for a further 4 hours then left to stand overnight. 2M hydrochloric acid (10 ml) is 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 an orange 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)-1,8,8-trimethylbicyclo[3.2.1]octane-2,4-dione (0.04 g, 9%) as a colourless 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. 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 an orange 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-e4d78bb20c3d472a8da8032aefd0e0a6
Source dataset
uspto-grants-2014_09
Patent number
US08828908B2

Reaction notes

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