Hydrochloric Acid → 3-Chloro-2,4,5-trifluorobenzoic Acid

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Reaction Steps

3-Amino-2,4,5-trifluorobenzoic acid (Example 2), 0.52 g, and 3 g of cupric chloride are added to 10 ml of a 3% aqueous solution of hydrochloric acid and the mixture is stirred with ice bath cooling. A solution of 0.32 g of sodium nitrite in 4 ml of water is added to the reaction mixture in portions over a one-hour period while maintaining the reaction at 0°-5° C. The ice bath is then removed and the mixture is stirred for two hours at room temperature. Toluene, 20 ml, and 15 ml of water are added with stirring. The layers are separated and the aqueous layer extracted with 20 ml of toluene. The combined toluene extracts are extracted with 4 ml of a 36% aqueous solution of hydrochloric acid and then concentrated to a solid under reduced pressure to give 0.48 g (83%) of 3-chloro-2,4,5-trifluorobenzoic acid as a tan solid; GC (98.4%); HPLC (89.2%); recrystallization from heptanes gives 0.40 g (70%) of 3-chloro-2,4,5-trifluorobenzoic acid; mp 109°-111° C.

Provenance & Evidence