Trifluoroacetic acid → 2-(4-(4-Nitro-3-(trifluoromethyl)phenylamino)cyclohexyloxy)acetic acid

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Reaction Conditions

Reaction Steps

4-(4-Nitro-3-trifluoromethyl-phenylamino)-cyclohexanol (2.79 mmol) is dissolved in dry tetrahydrofuran (7 mL) and sodium hydride (60% suspension in oil, 7.0 mmol) is added. The resulting mixture is stirred for 15 min and is cooled down to 5° C. prior to the addition of acetic acid tert-butyl ester (2.79 mmol). After 1.5 hours reaction time, water (5 mL) is slowly added under vigorous stirring and the mixture is then diluted with ethyl acetate (20 mL). The organic phase is collected and is concentrated under reduced pressure. The residue obtained is then treated with a 1 to 1 mixture of dichloromethane and trifluoroacetic acid (7 mL). After complete conversion of the intermediate ester into the desired acid, the reaction mixture is again concentrated under reduced pressure. The residue obtained is taken up in dichloromethane (20 mL) and the organic phase is extracted with aqueous 3N sodium hydroxide solution (10 mL). The organic phase is then washed with water (2×7 mL), and these aqueous phases are in turn extracted with dichloromethane (2×7 mL). The pH of all combined aqueous phases is then brought to 5-6 by the addition of aqueous 5N hydrochloric acid. The acidic aqueous phase is extracted with dichloromethane (2×15 mL) and the combined organic layers are dried over magnesium sulphate, filtered and concentrated under reduced pressure to afford the desired acid (59% yield).

Provenance & Evidence