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

Participants

Reaction Conditions

Reaction Steps

A 500 mL multi-neck flask with overhead stirrer, thermocouple and condenser was charged with 5-chloro-2-cyclopropyl-1,6-dihydro-6-oxo-4-pyrimidinecarboxylic acid (35.0 g, 0.163 mol), ethyl acetate (105 mL) and N,N-dimethylformamide (1.19 g, 0.016 mol) at room temperature. Thionyl chloride (48.5 g, 0.408 mol) was added at room temperature over 50 minutes, and the reaction mixture was heated at 68° C. for 7 h. The reaction mixture was cooled to 25° C. and added over 30 minutes into a 500-mL multi-neck flask containing water (100 mL) while maintaining the temperature at 10-20° C. The resulting mixture was stirred for additional 30 minutes, and the organic layer was separated from the aqueous layer. The aqueous layer was extracted with additional ethyl acetate (20 mL), and the combined organic layers were washed with water. The organic layer containing 35.0 g (93% yield) of the title product was directly carried over to the next step.

Provenance & Evidence