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

Temperature

80 °C

(1R*,5S*)-1-Methyl-8-oxabicyclo[3.2.1]octane-2,4-dione (0.20 g, 1.30 mmol) and 4-dimethylamino-pyridine (0.792 g, 6.49 mmol) are added to a mixture of chloroform (4 ml) and toluene (1 ml). The reaction mixture is flushed with nitrogen for 15 minutes at ambient temperature. 4′-Chloro-3,5-diethylbiphen-4-yllead triacetate (0.896 g, 1.43 mmol) is added in one portion and the reaction mixture is stirred and heated to 80° C. under an atmosphere of nitrogen for 1 hour. The reaction mixture is cooled to room temperature, acidified to pH 1 with 2N aqueous hydrochloric acid, filtered through a plug of diatomaceous earth and the two phases are separated. The aqueous phase is extracted with dichloromethane (2×5 ml), the organic phases are combined, washed with water, and dried over anhydrous sodium sulfate. The mixture is filtered, and the filtrate is evaporated under reduced pressure. The residue is purified by column chromatography on silica gel to give (1R*,5S*)-3-(4′-chloro-3,5-diethyl-biphenyl-4-yl)-1-methyl-8-oxabicyclo[3.2.1]octane-2,4-dione as a white solid (0.064 g).

1. customThe reaction mixture is flushed with nitrogen for 15 minutes at ambient temperature
2. temperatureThe reaction mixture is cooled to room temperature
3. filtrationfiltered through a plug of diatomaceous earth
4. customthe two phases are separated
5. extractionThe aqueous phase is extracted with dichloromethane (2×5 ml)
6. washwashed with water
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationThe mixture is filtered
9. customthe filtrate is evaporated under reduced pressure
10. customThe residue is purified by column chromatography on silica gel

ORD record

ord-10c4b6160aee4ce09f1de0cb3e3a7d2f

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08895761B2