Phosphorus oxybromide → 3-bromo-6-methyl-1-(3-(trifluoromethyl)phenyl)pyrazin-2(1H)-one

Participants

Reaction Conditions

Reaction Steps

6-Methyl-1-[3-(trifluoromethyl)phenyl]-1,4-dihydropyrazine-2,3-dione (289.34 g @ 100%, 1 eq) and toluene (3 L) were charged to a flask and the slurry heated to reflux. Azeotroped water (53 ml) was collected and the slurry cooled to 25° C. The toluene was then removed under reduced pressure at <50° C. to give an off-white powder. This material was then added to acetonitrile (2.95 L) and the reaction mixture heated to 64-67° C. In a separate 2 L 3 necked flask, phosphorus oxybromide (368.4 g, 1.2 eq) was dissolved in acetonitrile (1.475 L). The POBr3/acetonitrile solution was then added to the original flask over 45 minutes at 64-67° C. The reaction mixture was then held at 64-67° C. for 4.5 hours and was then cooled to 20-25° C. Saturated sodium bicarbonate in water (10.3 L) was added over 30 minutes to quench the reaction. The mixture was then stirred for 6 hours at 20-25° C. The solid was then filtered off and the filter-cake washed with water (2×0.55 L) to give the title compound as a water-wet solid (486.4 g, 74.3% @ 100%).

Provenance & Evidence