反应详情

温度

50 °C

A 5 L 4-neck flask equipped with N2 inlet/bubbler with H2O trap, overhead stirring, and an addition funnel was charged with 30% oleum (˜10.5 volumes, 2.2 L, 8×500 g bottles+100 mL), and heated to 50° C. under a slight N2 flow. 5-Hydroxy-2-adamantanone (220 g, 81 wt % purity, 1.07 mol) was dissolved in 5 volumes HCO2H (˜98%, 1.10 L) and added drop-wise to the warm oleum solution over 5 hours. The addition rate was adjusted to maintain the internal temperature between 70-90° C. After stirring an additional 2 hours at 70° C. The reaction solution was cooled to 10° C. in an ice bath. 20 volumes of 10% NaCl aq (4 L) were cooled to <10° C., the crude reaction mixture was quenched into the brine solution in batches, maintaining an internal temperature <70° C. The quenched reaction solution was combined with a second identical reaction mixture for isolation. The combined product solutions were extracted 3×5 volumes with CH2Cl2 (3×2.2 L) and the combined CH2Cl2 layers were then washed 1×2 volumes with 10% NaCl (1 L). The CH2Cl2 solution was then extracted 3×5 volumes with 10% Na2CO3 (3×2.2 L). The combined Na2CO3 extracts were washed with 1×2 volumes with CH2Cl2 (1 L). The Na2CO3 layer was then adjusted to pH 1-2 with concentrated HCl (˜2 volumes, product precipitates out of solution). The acidic solution was then extracted 3×5 volumes with CH2Cl2 (3×2.2 L), and the organic layer was washed 1×2 volumes with 10% NaCl. The organic solution was then dried over Na2SO4, filtered, concentrated to ˜1/4 volume, then chase distilled with 2 volumes EtOAc (1 L). Nucleation occurred during this distillation. The suspension was then chase distilled 2×5 volumes (2×2 L) with heptane and cooled to room temperature. The suspension was then filtered, and the liquors were recirculated 2× to wash the wet cake. The resultant material was dried overnight at 50° C., 20 mm Hg to afford the title compound.

1. customA 5 L 4-neck flask equipped with N2 inlet/bubbler with H2O trap
2. temperatureto maintain the internal temperature between 70-90° C
3. stirringAfter stirring an additional 2 hours at 70° C
4. temperatureThe reaction solution was cooled to 10° C. in an ice bath
5. customthe crude reaction mixture
6. customwas quenched into the brine solution in batches
7. temperaturemaintaining an internal temperature <70° C
8. customThe quenched reaction solution
9. extractionThe combined product solutions were extracted 3×5 volumes with CH2Cl2 (3×2.2 L)
10. washthe combined CH2Cl2 layers were then washed 1×2 volumes with 10% NaCl (1 L)
11. extractionThe CH2Cl2 solution was then extracted 3×5 volumes with 10% Na2CO3 (3×2.2 L)
12. washThe combined Na2CO3 extracts were washed with 1×2 volumes with CH2Cl2 (1 L)
13. extractionThe acidic solution was then extracted 3×5 volumes with CH2Cl2 (3×2.2 L)
14. washthe organic layer was washed 1×2 volumes with 10% NaCl
15. dry with materialThe organic solution was then dried over Na2SO4
16. filtrationfiltered
17. concentrationconcentrated to ˜1/4 volume
18. distillationchase distilled with 2 volumes EtOAc (1 L)
19. distillationNucleation occurred during this distillation
20. distillationThe suspension was then chase distilled 2×5 volumes (2×2 L) with heptane
21. temperaturecooled to room temperature
22. filtrationThe suspension was then filtered
23. washto wash the wet cake
24. dry with materialThe resultant material was dried overnight at 50° C.