Hydrochloric Acid → (1R*,5S*)-3-(4'-chloro-4-ethylbiphenyl-3-yl)-1-methyl-8-oxabicyclo[3.2.1]octane-2,4-dione

HRID 1191546Notes

Reaction equation

HRID 1191546 reaction equation
C(Cl)(Cl)Cl.[CH3:5][C@@:6]12[O:13][C@@H:10]([CH2:11][CH2:12]1)[C:9](=[O:14])[CH2:8][C:7]2=[O:15].C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Cl:28][C:29]1[CH:34]=[CH:33][C:32]([C:35]2[CH:40]=[CH:39][C:38]([CH2:41][CH3:42])=[C:37]([Pb+3])[CH:36]=2)=[CH:31][CH:30]=1.Cl>C1(C)C=CC=CC=1>[Cl:28][C:29]1[CH:30]=[CH:31][C:32]([C:35]2[CH:40]=[CH:39][C:38]([CH2:41][CH3:42])=[C:37]([CH:8]3[C:9](=[O:14])[C@H:10]4[O:13][C@:6]([CH3:5])([CH2:12][CH2:11]4)[C:7]3=[O:15])[CH:36]=2)=[CH:33][CH:34]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6212ChloroformHCID 67533518(1R*,5S*)-1-methyl-8-oxabicyclo[3.2.1]octane-2,4-dioneHCID 178476534HCID 178476534, compound

Product 1

HCID 68487113(1R*,5S*)-3-(4'-chloro-4-ethylbiphenyl-3-yl)-1-methyl-8-oxabicyclo[3.2.1]octane-2,4-dioneYield 67.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of chloroform (2.0 ml) and toluene (0.5 ml) is added (1R*,5S*)-1-methyl-8-oxa-bicyclo[3.2.1]octane-2,4-dione (0.10 g, 0.6 mmol) and N,N-dimethylamino-pyridine (0.395 g, 3.2 mmol) under a nitrogen atmosphere with stirring. To this reaction mixture is added 4′-chloro-4-ethylbiphenyl-3-yllead triacetate (0.42 g, 0.70 mmol) in one portion, then the mixture is heated at 80° C. for 1-2 hours. The reaction mixture is cooled to room temperature, acidified with dilute aqueous hydrochloric acid then filtered through diatomaceous earth to remove inorganic residues (subsequent washing with dichloromethane). The aqueous fractions are extracted with dichloromethane (2×5 ml), all organic fractions are combined, dried over sodium sulfate then concentrated under vacuum to give the crude product which is purified by flash chromatography (hexane/ethyl acetate) to give (1R*,5S*)-3-(4′-chloro-4-ethylbiphenyl-3-yl)-1-methyl-8-oxabicyclo[3.2.1]octane-2,4-dione (0.150 g) as a white solid.

Workup

  1. temperatureThe reaction mixture is cooled to room temperature
  2. filtrationthen filtered through diatomaceous earth
  3. customto remove inorganic
  4. washresidues (subsequent washing with dichloromethane)
  5. extractionThe aqueous fractions are extracted with dichloromethane (2×5 ml)
  6. dry with materialdried over sodium sulfate
  7. concentrationthen concentrated under vacuum
  8. customto give the crude product which
  9. customis purified by flash chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-766603ceb24f4ef6af6958fa51292acb
Source dataset
uspto-grants-2014_03
Patent number
US08680012B2

Reaction notes

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