Sulfuric Acid → 2-((1S,2R,5S)-6,6-dimethylbicyclo[3.1.1]heptan-2-yl)acetic acid

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Reaction Conditions

Reaction Steps

Concentrated sulfuric acid (33 mL) was added drop wise to ethanol (120 mL) at 0° C. A solution of Example 21B (7.20 g, 44.1 mmol) in ethanol (20 mL) was added to the ethanol-H2SO4 mixture. The mixture was heated at reflux for 24 hours. TLC showed a 1/1 mixture of ethyl ester and acid. The mixture was diluted with water. Ethanol was evaporated under reduced pressure and the mixture was extracted with ether. The organic extracts were dried with magnesium sulfate, filtered, and concentrated. The residue was dissolved in tetrahydrofuran (50 mL). To the mixture was added a solution of 25% NaOH (10 mL). The reaction was heated at 40° C. for 12 hours. The mixture was cooled at room temperature, tetrahydrofuran was evaporated, the mixture was diluted with brine and washed with ether (2×25 mL). The aqueous phase was acidified to pH 2 with 5 N HCl and extracted with ether (3×75 mL). The organic extracts were dried over magnesium sulfate, filtered, and concentrated to give the title compound.

Provenance & Evidence