[Synthesis]
Methyl 3,5-dichlorobenzoate (14.66 g, 71.5 mmol) was used as a raw material, and was mixed with zinc cyanide (5.04 g, 42.9 mmol), zinc powder (0.21 g, 3.21 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride complex with dichloromethane (1:1) (1.3 g, 1.57 mmol) in N ,N-dimethylformamide (70 mL) was mixed and heated to reflux for 5 hours. After completion of the reaction, it was cooled to room temperature, the reaction mixture was diluted with ethyl acetate and extracted sequentially with water and brine. Purification by silica gel column chromatography afforded 2.34 g (17% yield) of methyl 2-chloro-5-cyanobenzoate. The intermediate ester was dissolved in methanol (50 mL), 4 N sodium hydroxide solution (7.5 mL, 30 mmol) was added, and stirred at room temperature for 18 hours. At the end of the reaction, the solvent was removed under vacuum, the residue was dissolved in ethyl acetate and the organic phase was washed sequentially with 5% HCl and brine. Finally, the solvent was removed to give 1.8 g (83% yield) of 3-chloro-5-cyanobenzoic acid. |