Phosphorus tribromide → HCID 66905965, compound

Participants

Reaction Conditions

Reaction Steps

A 1-L, three-necked flask equipped with an addition funnel, thermometer, condenser, nitrogen bubbler, and caustic scrubber was charged with 5-chloro-2-[(ethoxy-carbonyl)amino]-3-methylbenzoic acid (i.e. the product of Reference Example 1) (74.0 g, 0.288 mol) and toluene (300 mL). The mixture was heated at 60-65° C. while phosphorus tribromide (39 g, 0.144 mol) was added over about 60 minutes. The mixture was heated at 65° C. for about 30 minutes, which resulted in no more than 0.2% of the intermediate 6-chloro-2-ethoxy-8-methyl-4H-3,1-benzoxazin-4-one remaining according to HPLC analysis. The mixture was sparged with nitrogen to remove hydrogen bromide and ethyl bromide, and then cooled to 20° C. The product was collected under filtration, and the filter cake was successively washed with toluene (30 mL) and water (2×100 mL), and then suction dried. Drying the collected solid in a vacuum oven to constant weight provided the title compound (59 g, about 97% purity by HPLC analysis). A portion of the dried product was recrystallized by dissolving in N,N-dimethylformamide (4 volumes) at 60° C. and cooling to 20° C. to provide a sample of 99% purity melting at >250° C.

Provenance & Evidence