Hydrochloric Acid → HCID 178500110, compound

Participants

Reaction Conditions

Reaction Steps

Charge anhydrous methanol (50 mL) to a flask followed by sodium methoxide (5.4 g, 0.1 mol, 0.3 equiv) and heat the mixture to 65-70° C. Add propanedioic acid dimethyl ester (44 g, 0.33 mol, 1.0 equiv) drop wise and the stir mixture at 65-70° C. for 10-30 min. Add ethyl crotonate (33.4 g, 0.33 mol, 1.0 equiv) drop wise over 1-2 h, and stir the mixture at 65-70° C. for 1-1.5 h. Cool the reaction mixture to −20° C. to −10° C. In a separate flask, dissolve sodium methoxide (54 g, 1.0 mol, 3.0 equiv) in anhydrous methanol (180 mL) and stir the mixture for 20-30 min. Cool the mixture to −20° C. to −10° C., and add formamidine acetate (40 g, 0.4 mol, 1.2 equiv). Add this solution drop wise to the first solution over a period of 1 h while maintaining the temperature from −20° C. to −10° C. Stir for 1-2 h and then warm the mixture to 20-25° C. over 3-4 h. Stir the mixture for 2-8 h, and then charge a solution of concentrated HCl (110-130 g) in water (330 g-390 g) while keeping the reaction temperature <10° C. Stir the suspension for 30-60 min at <10° C. and filter. Wash the filter cake with water (70 mL) and slurry the filter cake with methanol (56 g). Filter to collect methyl 3-(4,6-dihydroxypyrimidin-5-yl)butanoate (55.6 g, 72%). MS (ES) m/z=213 [M]+.

Provenance & Evidence