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

Temperature

40 °C

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.

1. temperatureThe mixture was heated
2. temperatureat reflux for 24 hours
3. customEthanol was evaporated under reduced pressure
4. extractionthe mixture was extracted with ether
5. dry with materialThe organic extracts were dried with magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. dissolutionThe residue was dissolved in tetrahydrofuran (50 mL)
9. additionTo the mixture was added a solution of 25% NaOH (10 mL)
10. temperatureThe mixture was cooled at room temperature
11. customtetrahydrofuran was evaporated
12. additionthe mixture was diluted with brine
13. washwashed with ether (2×25 mL)
14. extractionextracted with ether (3×75 mL)
15. dry with materialThe organic extracts were dried over magnesium sulfate
16. filtrationfiltered
17. concentrationconcentrated

ORD record

ord-0c6d430143534843a6159d485e642904

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08609674B2