反应详情

To a 2 ml THF solution of ethyl 7-(3-(2-propyl-4-phenoxyphenoxy)propoxy)-chromane-2-carboxylate (Example 1, Step B) (100 mg, 0.204 mmol) were added hexamethylphosphoramide (0.046 ml, 0.26 mmol) and sodium bis(trimethylsilyl)amide (1.0M THF solution) (0.265 ml, 0.265 mmol) upon cooling in a dry ice-acetone bath. After stirring at that temperature for 30min, to it was added iodopropane (0.06 ml, 6.2 mmol). The cooling bath was removed and the reaction mixture was gradually warmed to rt overnight. The solvent was removed under reduced pressure, diluted with AcOEt and water. The organic layer was separated. The aqueous layer was extracted twice with AcOEt. The combined organic layers were dried over anhydrous Na2SO4, filtered, concentrated, and chromatographed on silica gel. Elution with 5% AcOEt/hexanes gave the title compound as a clear oil 33 mg (30%).

1. temperatureupon cooling in a dry ice-acetone bath
2. customThe cooling bath was removed
3. customThe solvent was removed under reduced pressure
4. additiondiluted with AcOEt and water
5. customThe organic layer was separated
6. extractionThe aqueous layer was extracted twice with AcOEt
7. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customchromatographed on silica gel
11. washElution with 5% AcOEt/hexanes