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0 °C

A solution of 4-hydroxy-2-tert-butyl-pyrimidine-5-carboxylic acid ethyl ester (3 g, 13.377 mmol, prepared in an analogous manner as described for the preparation of 2-ethyl-4-hydroxy-pyrimidine-5-carboxylic acid ethyl ester, Dostert, P. et al. Eur. J. Med. Chem. 1982, 17, 437-444) in dimethylformamide (10 mL) was added slowly to the suspension of sodium hydride (800 mg, 60% in mineral oil, Aldrich) in dimethylformamide cooled to 0° C. After the addition, the ice bath was removed and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was stirred at room temperature for 4 h then quenched with saturated solution of ammonium chloride. It was extracted with ethyl acetate (2×). The organic extracts were washed with brine (1×), dried over anhydrous sodium sulfate and concentrated. Purification of the crude residue by flash column chromatography (120 g of silica gel, eluting with a gradient of 5-60% ethyl acetate in hexane gave 4-ethoxy-2-tert-butyl-pyrimidine-5-carboxylic acid ethyl ester (1.12 g, 30%).

1. additionAfter the addition
2. customthe ice bath was removed
3. stirringThe reaction mixture was stirred at room temperature for 4 h
4. customthen quenched with saturated solution of ammonium chloride
5. extractionIt was extracted with ethyl acetate (2×)
6. washThe organic extracts were washed with brine (1×)
7. dry with materialdried over anhydrous sodium sulfate
8. concentrationconcentrated
9. customPurification of the crude residue by flash column chromatography (120 g of silica gel
10. washeluting with a gradient of 5-60% ethyl acetate in hexane