反应详情

(1,4-Dioxa-spiro[4.5]dec-8-yl)-methanol (from Example 33, 765 mg, 4.44 mmol) in DMF (3 mL) at 0° C. was treated with NaH (Aldrich, 60% in mineral oil, 355 mg, 8.88 mmol) followed by EtI (Aldrich, 0.7 mL, 8.88 mmol). The resulting solution was slowly warmed to room temperature for 2 hours and heated at 60° C. for additional 30 min. The solution was then partitioned between ethyl acetate and saturated NH4Cl. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to give the crude material, which was treated with 1N HCl (2 mL) and acetone (6 mL) at room temperature for 2 hours. The solvent was removed and the solution was then partitioned between ethyl acetate and saturated NaHCO3. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to give the crude material, purified by silica gel column (hexanes:ethyl acetate 5:1) to afford the title compound as colorless solid.

1. temperatureheated at 60° C. for additional 30 min
2. customThe solution was then partitioned between ethyl acetate and saturated NH4Cl
3. washThe combined organic layers were washed with brine
4. dry with materialdried over anhydrous Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customto give the crude material, which
8. customThe solvent was removed
9. customthe solution was then partitioned between ethyl acetate and saturated NaHCO3
10. washThe combined organic layers were washed with brine
11. dry with materialdried over anhydrous Na2SO4
12. filtrationfiltered
13. concentrationconcentrated
14. customto give the crude material
15. custompurified by silica gel column (hexanes:ethyl acetate 5:1)