Hexamethylphosphoramide → Ethyl 7-(3-(2-propyl-4-phenoxyphenoxy)propoxy)-2-propylchromane-2-carboxylate

Participants

Reaction Steps

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%).

Provenance & Evidence