Hydrochloric Acid → (1R*,5S*)-3-(4-bromo-2-ethylphenyl)-1-methyl-8-oxabicyclo[3.2.1]octane-2,4-dione

Temperatur

80 °C

(1R*,5S*)-1-Methyl-8-oxabicyclo[3.2.1]octane-2,4-dione (6 g, 38.96 mmol) and 4-dimethylaminopyridine (23.76 g, 194.75 mmol) are added to a mixture of chloroform (120 ml) and toluene (30 ml). The reaction mixture is flushed with nitrogen for 15 minutes at ambient temperature. 4-Bromo-2-ethylphenyllead triacetate (24.3 g, 42.85 mmol) is added in one portion and the reaction mixture is stirred and heated to 80° C. (pre-heated oil bath) 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 separated. The aqueous phase is extracted with dichloromethane (2×50 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-bromo-2-ethylphenyl)-1-methyl-8-oxabicyclo[3.2.1]octane-2,4-dione as a white solid (6 g).

1. customThe reaction mixture is flushed with nitrogen for 15 minutes at ambient temperature
2. temperature(pre-heated oil bath) under an atmosphere of nitrogen for 1 hour
3. temperatureThe reaction mixture is cooled to room temperature
4. filtrationfiltered through a plug of diatomaceous earth
5. customthe two phases separated
6. extractionThe aqueous phase is extracted with dichloromethane (2×50 ml)
7. washwashed with water
8. dry with materialdried over anhydrous sodium sulfate
9. filtrationThe mixture is filtered
10. customthe filtrate is evaporated under reduced pressure
11. customThe residue is purified by column chromatography on silica gel

ORD-Eintrag

ord-8d88638a538c48268e8671cb769ec0df

Quelldatensatz

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08895761B2