Water → 5,6-Dichloro-2-cyclopropylpyrimidine-4-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

Phosphorus oxychloride (363 g, 221 mL, 2.37 mol) and 5-chloro-2-cyclopropyl-1,6-dihydro-6-oxo-4-pyrimidinecarboxylic acid (169 g, 0.79 mol) were added to a 1-L flask and heated at 90° C. for 5 h. The reaction mixture was cooled to 30° C. and added over 60 minutes into a 2-L jacketed reactor containing a well-stirred mixture of t-butanol (280 mL) and water (750 mL) while maintaining the temperature at 5-10° C. After the addition of the reaction mixture was about 70% complete, the aqueous t-butanol mixture was seeded to initiate crystallization, and the addition of the reaction mixture was continued. At the end of the addition, water (750 mL) was added gradually at 10-15° C., and the mixture was stirred for an additional 1 h. The resulting mixture was cooled to 5° C., filtered, and the collected solid was washed with water (3×50 mL). The resulting wet cake was dried in a vacuum-oven at 60° C. to give 156 g (85% yield) of the title compound as a solid melting at 126-127° C.

Provenance & Evidence