Hydrochloric Acid → 2-(2-Ethyl-5-hydroxyphenyl)hexahydro-4,7-ethanoindene-1,3-dione

HRID 339466Notes

Reaction equation

HRID 339466 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:21][CH3:22])=[C:6]([CH:8]2[C:16](=[O:17])[CH:15]3[CH:10]([CH:11]4[CH2:19][CH2:18][CH:14]3[CH2:13][CH2:12]4)[C:9]2=[O:20])[CH:7]=1.N1CCC[C@H]1C(O)=[O:26].[OH-].[Na+].Cl>C(OCC)(=O)C.[Cu]I>[CH2:21]([C:5]1[CH:4]=[CH:3][C:2]([OH:26])=[CH:7][C:6]=1[CH:8]1[C:9](=[O:20])[CH:10]2[CH:15]([CH:14]3[CH2:18][CH2:19][CH:11]2[CH2:12][CH2:13]3)[C:16]1=[O:17])[CH3:22]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 145742L-ProlineHCID 666771442-(5-Bromo-2-ethylphenyl)-3a,4,5,6,7,7a-hexahydro-4,7-ethanoindene-1,3-dione

Product 1

HCID 666778142-(2-Ethyl-5-hydroxyphenyl)hexahydro-4,7-ethanoindene-1,3-dione

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
200 °C

Procedure

To a solution of 2-(5-bromo-2-ethylphenyl)-3a,4,5,6,7,7a-hexahydro-4,7-ethanoindene-1,3-dione (1.01 g, 2.8 mmol), copper (I) iodide (108 mg, 0.57 mmol) and L-proline (33 mg, 0.28 mmol) is added a solution of 1M aqueous sodium hydroxide (8.8 mL, 8.8 mmol), and the mixture is then heated at 200° C. for 150 minutes under microwave irradiation. After cooling to room temperature the mixture is diluted with ethyl acetate and then acidified with 2M hydrochloric acid and filtered through diatomaceous earth (washing with additional ethyl acetate). The aqueous phase is extracted into ethyl acetate (×3) and the combined organic extracts are washed with brine, dried over magnesium sulfate, filtered and the filtrate concentrated under reduced pressure. The residue is purified by flash column chromatography on silica gel (ethyl acetate/iso-hexane eluant) to afford 2-(2-ethyl-5-hydroxyphenyl)hexahydro-4,7-ethanoindene-1,3-dione.

Workup

  1. temperatureAfter cooling to room temperature the mixture
  2. filtrationfiltered through diatomaceous earth (washing with additional ethyl acetate)
  3. extractionThe aqueous phase is extracted into ethyl acetate (×3)
  4. washthe combined organic extracts are washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated under reduced pressure
  8. customThe residue is purified by flash column chromatography on silica gel (ethyl acetate/iso-hexane eluant)

Sources & evidence

ORD record
ord-0dfa70cc06344d5bba304e04dd26696b
Source dataset
uspto-grants-2014_11
Patent number
US08895474B2

Reaction notes

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