Hydrochloric Acid → 2,4,6-Trimethyl-pyrimidine-5-carboxylic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

Methyl 2-acetyl-3-methoxy-2-butenoate (34.4 g, 0.2 mole), acetamidine hydrochloride (22.7 g), acetone (136 ml) and methyl alcohol (100 ml) were charged into a 1 L 3-necked, flask (fitted with addition funnel, condenser, agitator and nitrogen inlet). The reaction was blanketed with nitrogen, the agitator started and the batch cooled to between −5 and 0° C. While the batch was cooling, a solution of potassium t-butoxide was prepared (27 g in THF, 100 ml) under nitrogen. When the batch reached the correct temperature, the potassium t-butoxide solution was slowly charged, keeping the temperature below 5° C. The batch was allowed to warm to about 25° C. The reaction was complete after about 1.5 hours. Concentrated hydrochloric acid was charged dropwise to bring the pH to 7. The batch was concentrated under vacuum until no more volatiles were collected. Methyl t-butylether (140 ml) and water (85 ml) were charged. The batch was agitated for 10 minutes and the layers were then separated. The organic layer was concentrated under vacuum to afford a solid residue of methyl 2,4,6-trimethylpyrimidine-5-carboxylate, 35.8 g. The product was purified by crystallizing from methanol. m. p. 61–62° C., 1H NMR (CDCl3): δ2.44 (6H, s, CH3), δ2.61 (3H, s, CH3), δ3.88 (3H, s, OCH3). 13H CMR (CDCl3): δ168.57, δ168.00, δ164.83, δ123.71, δ52.87, δ26.38, δ23.26. HR-MS; Calculated for C9H13N2O2, m/z=181.0977. Found 181.0972.

Provenance & Evidence