4,6-Dimethylpyrimidin-2-ol → Methyl 2-Phenoxy-2-((4,6-dimethylpyrimidin-2-yl)oxy)acetate

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Reaction Steps

4,6-Dimethyl-2-pyrimidinol (3.0 g, 24 mmol) and 60 mL of tetrahydrofuran were placed in a dry 250 mL flask and blanketed with argon. Sodium hydride (1.0 g of 60 percent, 24 mmol) was added carefully and the mixture was allowed to stir at ambient temperature for 0.5 hr. A solution of methyl 2-bromo-2-phenoxyacetate (7.2 g, 29 mmol) in a small amount of tetrahydrofuran was added dropwise with stirring and the mixture was then allowed to stir overnight under argon at ambient temperature. The resulting mixture was found by thin layer chromatography to contain only a trace of the starting pyrimidinol. The mixture was concentrated by evaporation under reduced pressure and the residue was diluted with water and ether. The phases that formed were separated and the aqueous phase was extracted twice with ether. The combined ethereal phase was extracted with water and then dried over magnesium sulfate, filtered, and concentrated by evaporation under reduced pressure to obtain the title compound in crude form as a reddish oil. This oil was column chromatographed on silica eluting with a 75:25 mixture of hexane and ethyl acetate to obtain 1.2 g (17 percent of theory) of the title compound as a pink oil of 93 percent purity, as determined by gas-liquid chromatography.

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