N-methyl-2-pyrrolidone → 2,4,5-Trifluorobenzoic acid

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Reaction Steps

A 250 mL single-neck flask equipped with a condenser and a magnetic stirrer was charged with 30.00 g of 3,4,6-trifluorophthalic acid, and 200 mL of NMP. The reaction mixture was then heated with stirring for 18 hr. at a bath temperature of 140° C., followed by 55 hr. at a bath temperature of 150° C. The flask was then allowed to cool to room temperature and the contents were poured into 500 mL of water, and extracted with 4×200 mL of ethyl acetate. The combined organic extracts were washed with water (2×200 mL), dried over magnesium sulfate, filtered, and the solvent removed on a rotary evaporator followed by drying at the pump overnight. The crude product (24.25 g) was then dissolved in 25 mL of ethyl acetate and introduced at the top of a silica column (4.5 cm ID×56 cm, flushed with hexane). The product was then eluted with 90:10 hexane:ethyl acetate under a slight nitrogen pressure, and the fractions (500 mL each) were monitored by gas chromatography. The fractions containing the product were combined, the solvent removed on a rotary evaporator, and then dried at the pump overnight to give 2,4,5-trifluorobenzoic acid as a light yellow solid (21.06 g, 98.97% pure, 87.8% yield). Recrystallization of the product from toluene (50 mL, ca. 60° C.) gave a white product (71.1% overall yield) mp 101°-102° C.

Provenance & Evidence