Ammonia → 2-Amino-4,5-difluorobenzoic acid

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Dimethoxyethane (43 parts) was charged to a reactor and ammonia was bubbled in to form a saturated solution. The ammonia addition was maintained while a solution of 1.84 parts of 4,5-difluorophthalic anhydride in 13 parts of dimethoxyethane was added slowly over a period of 0.5 hours. The reaction mixture was stirred for an additional 5 minute period and the dimethoxyethane was removed by vacuum distillation. The remaining white solid (the ammonium salt of 4,5-difluorophthalamic acid) was dissolved in 20 parts of aqueous sodium hydroxide (40% NaOH) and the solution was de-gassed under moderately reduced pressure to remove any remaining ammonia; then heated at atmospheric pressure, to 50° C. and maintained at tha temperature while 14.1 parts of a 5.78% aqueous sodium hypochlorite solution was added. The solution was then heated to 60°-65° C. and maintained at that temperature, with stirring for about 30 minutes; then cooled to about 20°-25° C. and acidified to a pH of 4-6, by addition of concentrated hydrochloric acid. A precipitate formed and the mixture was extracted with chloroform. The acidification procedure was repeated until no additional precipitate formed. The combined extracts were dried over anhydrous sodium sulfate, filtered, and the chloroform removed by vacuum distillation to yield 1.34 parts of solid 4,5-difluoroanthranilic acid having a melting point of 180°-181° C. The chemical structure of the product was confirmed by infra-red analysis.

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