反应详情

tert-Butyl 3-oxocyclohexanecarboxylate (1.35 g, 6.81 mmol) was taken up in water (11.4 mL) and stirred at ambient temperature. Sodium metabisulfite (0.75 g, 3.9 mmol) was added and the mixture was allowed to stir for 40 minutes. Diethyl ether (11.4 mL) was added, followed by potassium cyanide (0.70 g, 11 mmol). The resulting mixture was allowed to stir vigorously for 1 hour before it was partitioned between diethyl ether and water. The organic layer was washed with water, brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue, used without further purification, was dissolved in DCM (22.0 mL). DIPEA (1.07 g, 8.26 mmol) was added and the resulting mixture was cooled to 0° C. Methanesulfonyl chloride (0.69 g, 6.1 mmol) was added dropwise and the resulting mixture was maintained at 0° C. for 20 minutes then allowed to warm to ambient temperature. The mixture was partitioned between DCM and water. The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue, used without further purification, was dissolved in pyridine (13.6 mL) and heated to 95° C. for 20 hours. The mixture was then allowed to cool to ambient temperature and was concentrated in vacuo. The residue was purified by MPLC on silica gel (using a gradient elution of 0-45% EtOAc/hexanes). Desired fractions were identified, combined, and concentrated in vacuo to afford the title compound. 1H NMR (500 MHz, CDCl3): δ 6.63-6.58 (m, 1H), 2.54-2.48 (m, 1H), 2.44-2.40 (m, 2H), 2.36-2.16 (m, 2H), 2.02-1.94 (m, 1H), 1.71-1.63 (m, 1H), 1.44 (s, 9H).

1. stirringto stir for 40 minutes
2. stirringto stir vigorously for 1 hour before it
3. customwas partitioned between diethyl ether and water
4. washThe organic layer was washed with water, brine
5. dry with materialdried over anhydrous MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue, used without further purification
9. dissolutionwas dissolved in DCM (22.0 mL)
10. temperaturethe resulting mixture was cooled to 0° C
11. temperaturethe resulting mixture was maintained at 0° C. for 20 minutes
12. temperatureto warm to ambient temperature
13. customThe mixture was partitioned between DCM and water
14. dry with materialThe organic layer was dried over anhydrous Na2SO4
15. filtrationfiltered
16. concentrationconcentrated in vacuo
17. customThe residue, used without further purification
18. dissolutionwas dissolved in pyridine (13.6 mL)
19. temperatureheated to 95° C. for 20 hours
20. temperatureto cool to ambient temperature
21. concentrationwas concentrated in vacuo
22. customThe residue was purified by MPLC on silica gel (
23. washa gradient elution of 0-45% EtOAc/hexanes)
24. concentrationconcentrated in vacuo