Dimethylformamide → (E)-(2-((6-Chloro-5-fluoropyrimidin-4-yl)oxy)phenyl)(5,6-dihydro-1,4,2-dioxazin-3-yl)methanone O-methyl oxime

Participants

Reaction Conditions

Reaction Steps

To a solution of 4,6-dichloro-5-fluoropyrimidine (DCFP) (100 g, 0.564 mol) in toluene (500 mL) was added (E)-(5,6-dihydro-1,4,2-dioxazin-3-yl)(2-hydroxyphenyl)methanone O-methyl oxime (13) (77.8 g, 0.466 mol), K2CO3 (76 g, 0.55 mol), followed by the addition of DMF (50 mL) at ambient temperature. The reaction mixture was stirred at 80-85° C. for 1-2 h. The progress of the reaction was monitored by the HPLC analysis. Upon completion of the reaction, the reaction mixture was washed with water (500 mL) and 10% brine solution (250 mL) to obtain the product in toluene layer meeting the desired specifications. Yield—88-98%.

Provenance & Evidence