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

HRID 1470854Notes

Reaction equation

HRID 1470854 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]([CH3:41])=[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]([CH3:41])=[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 178476525HCID 178476525, compound

Product 1

HCID 68481554(1R*,5S*)-3-(4'-chloro-4-methylbiphenyl-3-yl)-1-methyl-8-oxabicyclo[3.2.1]octane-2,4-dioneYield 41.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a mixture of chloroform (3.5 ml) and toluene (0.75 ml) is added (1R*,5S*)-1-methyl-8-oxa-bicyclo[3.2.1]octane-2,4-dione (0.25 g, 1.62 mmol) and N,N-dimethylaminopyridine (0.99 g, 8.11 mmol) under a nitrogen atmosphere with stirring. To this reaction mixture is then added 4′-chloro-4-methylbiphenyl-3-yllead triacetate (1.05 g, 1.78 mmol) in one portion, then the mixture 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). Aqueous fractions are extracted with dichloromethane (2×10 ml), then all organic fractions are combined, dried over sodium sulfate and concentrated under vacuum to give crude product which is purified by flash chromatography (hexane/ethyl acetate) to give (1R*,5S*)-3-(4′-chloro-4-methylbiphenyl-3-yl)-1-methyl-8-oxabicyclo[3.2.1]octane-2,4-dione (0.240 g) as a white solid.

Workup

  1. filtrationthen filtered through diatomaceous earth
  2. customto remove inorganic
  3. washresidues (subsequent washing with dichloromethane)
  4. extractionAqueous fractions are extracted with dichloromethane (2×10 ml)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customto give crude product which
  8. customis purified by flash chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-c60f35900fe541a3b1ef8d1a5ea6e1fe
Source dataset
uspto-grants-2015_04
Patent number
US09006429B2

Reaction notes

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