Hydrochloric Acid → 4-(Benzylamino)-3,5-difluoro-2,6-dimethoxybenzoic acid

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Reaction Conditions

Reaction Steps

Methyl 4-(benzylamino)-3,5-difluoro-2,6-dimethoxybenzoate (24.0 g) was dissolved in ethanol (75 mL) and the solution stirred and cooled to 10° C. under a nitrogen atmosphere. Sodium hydroxide, 50% aqueous solution (12.5 g, 156 mmol) was added dropwise over 10 minutes at 10° C.–15° C. followed by ethanol (10 mL). The solution was stirred at 15° C.–25° C. A thick precipitate formed. Stirring was continued for a total of 2 hours at 15° C.–25° C. The mixture was heated to 50° C.–55° C. where it was held for 1.5 hours. The mixture was allowed to cool to room temperature and held overnight. Water (100 mL) was added and the resulting solution cooled in an ice bath and acidified with 37% HCl (13.5 mL) to pH 2. The mixture was extracted with toluene (100 mL) and methyl tert-butyl ether (100 mL) and the organic extract washed with water (10 mL) and concentrated to an oil. This was triturated with toluene (20 mL) to give crystals which were collected and vacuum dried at 45° C. to give 4-(benzylamino)-3,5-difluoro-2,6-dimethoxybenzoic acid (19.4 g, 60 mmol): mp: 85° C.–86° C. (decomposition with gas evolution).

Provenance & Evidence