Synthesis
General procedure for the synthesis of 1-(6-methylpyridin-3-yl)-2-(4-(methylthio)phenyl)ethanone from 6-methylnicotinic acid methyl ester and 4-methylthiobenzeneacetic acid: 11 g of 4-methylthiobenzeneacetic acid and 200 mL of anhydrous THF were added to a reaction flask and the mixture was heated to 65-70 °C. While maintaining the temperature at 65-70 °C, 175 mL of a 1.0 M t-BuMgCl solution of THF and 5.7 g of 6-methylnicotinic acid methyl ester dissolved in 50 mL of THF were slowly added dropwise. After the dropwise addition was completed, the reaction was continued with stirring at 65-70°C for 1 hour. Upon completion of the reaction, the mixture was cooled to room temperature and 50 mL of 4 M hydrochloric acid was added slowly and dropwise to quench the reaction. The organic and aqueous layers were separated and the aqueous layer was extracted with 50mL of 4M hydrochloric acid. The aqueous layer was combined, 50g of sodium hydroxide was added and the reaction was heated to 40-50°C for 3 hours. After cooling to room temperature, filtration gave 6.9 g of light yellow solid product in 72.0% yield and 97.3% purity.
