Hydrochloric Acid → Aminocyclopyrachlor-methyl

Participants

Reaction Conditions

Reaction Steps

A 1-L flask equipped with a nitrogen bubbler connected to a trap and caustic-containing scrubber, an addition funnel, reflux condenser and thermocouple, was charged with 6-amino-5-chloro-2-cyclopropyl-4-pyrimidinecarboxylic acid monohydrate (144 g, 0.62 mol) and methanol (500 mL). Thionyl chloride (185 g, 115 mL, 1.58 mol) was added over about 30 minutes with cooling, and then the reaction mixture was heated at 60° C. for 12 h. The resulting mixture was concentrated at 40-45° C./6 kPa to remove excess methanol (about 300 mL), and the reaction mixture was diluted with water (580 mL). Phenolphthalein (5 mg) was added, and 50% aqueous NaOH (80 g, 1.0 mol) was added dropwise with cooling at 10-25° C. to bring the pH to about 9 as indicated by appearance of pink color. Then just enough 1 N aqueous hydrochloric acid was added to extinguish the pink color. The resulting slurry was cooled to 5° C. and filtered. The filtered wet cake was washed with water and dried to constant weight at 50° C./6 kPa to give 123 g (80% yield) of the title compound with 98% purity by HPLC analysis as a solid melting at 147-148° C.

Provenance & Evidence