2-Chloro-5-methylsulfanylbenzoic acid

886973-19-9

544-92-3

127510-97-8

51546-12-4

Methyl 2-chloro-5-(methylthio)benzoate (23.2 g, 106.9 mmol) and cuprous cyanide (19.2 g, 213.8 mmol) were dissolved in 100 mL of N-methylpyrrolidone. The reaction mixture was heated at 160 °C for 72 hours. The progress of the reaction was monitored by LCMS, which showed the presence of cyanide ester and hydrolyzed acid in a 1:1 ratio. Upon completion of the reaction, the mixture was cooled to room temperature and subsequently treated with 250 mL of water and 300 mL of ethyl acetate and filtered through diatomaceous earth. After separating the organic and aqueous phases, the aqueous phase was extracted with 2 x 250 mL of ethyl acetate. The organic phases were combined, washed with 250 mL of water, dried over MgSO4 and concentrated to give an oily crude product. The crude product was purified by combi fast silica gel column chromatography using a hexane solution of 0-20% ethyl acetate as eluent, resulting in methyl 2-cyano-5-(methylthio)benzoate (6.14 g, 28% yield) as a white solid.The LCMS analysis showed the following: retention time (Rt) = 2.42 min; mass-to-charge ratio (m/z) [M + H]+ = 208.