5462-71-5

1197-55-3

5462-71-5

The general procedure for the synthesis of 4-cyano-phenylacetic acid from p-aminophenylacetic acid was as follows: a suspension of 4-aminophenylacetic acid (18.2 g, 120.4 mmol), concentrated hydrochloric acid (24.7 mL), and water (90 mL) was preheated by passing it through a water bath at 40 °C, and acetic acid (13 mL) was subsequently added. The mixed solution was cooled to 0-5 °C via an ice-water bath and a solution of sodium nitrite (9 g, 130.4 mmol) in water (32 mL) was added slowly and dropwise over 20 min. The reaction temperature was maintained at 0-5 °C and stirring was continued for 25 min to obtain an orange solution. Subsequently, the above solution was slowly added to a mixed solution of sodium cyanide (29.5 g, 602 mmol), copper cyanide (21.6 g, 241 mmol), and water (280 mL) that had been pre-cooled to 4-5°C over a period of 40 minutes using a glass pipette (10 mL). The reaction mixture was stirred at 4°C for 1 hour and then continued to stir at room temperature for 2 hours. After completion of the reaction, the black suspension was filtered through diatomaceous earth and the precipitate was washed with ethyl acetate (50 mL, twice). The filtrate was extracted three times with ethyl acetate. All organic layers were combined and dried with anhydrous sodium sulfate, followed by concentration under reduced pressure to remove the solvent. The residue was purified by column chromatography (silica gel, 20% ethyl acetate solution in methanol) to give 4-cyanophenylacetic acid (15.3 g, 78.9% yield) as a yellow solid.