Cesium carbonate → HCID 86703469, compound

Temperature

70 °C

To a solution of 2-adamantanol (3.09 g, 20.26 mmol) in anhydrous dimethylsulfoxide (40 mL) was added tert-butyl 5-chloro-2,4-difluorobenzoate (6.56 g, 26.38 mmol) and cesium carbonate (13.20 g, 40.51 mmol), and the reaction mixture was heated at 70° C. for 16 hours. The solution was then cooled to ambient temperature and charged with an additional portion of 2-adamantanol (0.51 g, 3.34 mmol) and the reaction mixture was heated at 70° C. for an additional 24 hours. This process was repeated twice by addition of 2-adamantanol (0.49 g, 3.21 mmol) and (0.51 g, 3.31 mmol) respectively over an additional 48 hours. The mixture was cooled to ambient temperature and diluted with water (300 mL) and extracted with ethyl acetate (4×100 mL). The combined organic layers were washed with water (100 mL) and brine (100 mL); dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was recrystallized from hexanes and then triturated with methanol to give the title compound (1.63 g, 16%): 1H NMR (300 MHz, CDCl3) δ 7.88 (d, J=7.8 Hz, 1H), 6.62 (d, J=12.5 Hz, 1H), 4.49 (br s, 1H), 2.20-2.10 (m, 4H), 1.99-1.68 (m, 10H), 1.57 (s, 9H).

1. temperatureThe solution was then cooled to ambient temperature
2. temperaturethe reaction mixture was heated at 70° C. for an additional 24 hours
3. temperatureThe mixture was cooled to ambient temperature
4. extractionextracted with ethyl acetate (4×100 mL)
5. washThe combined organic layers were washed with water (100 mL) and brine (100 mL)
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe residue was recrystallized from hexanes
10. customtriturated with methanol

ORD record

ord-ce6aa0fc85e64cba9f6d369e1fd7a82c

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952169B2