Synthesis
The general procedure for the synthesis of ethyl 2-(6-chloropyridin-2-yl)acetate from 2-chloro-6-methylpyridine and diethyl carbonate was as follows: referring to the method of Example 6, n-butyllithium (23% hexane solution, 13.2 mL, 47.3 mmol) was added slowly and dropwise to a cold solution of 2-chloro-6-methylpyridine (5.0 g, 39.4 mmol) in tetrahydrofuran (30 mL) ( -70°C) and stirred at -70°C for 30 min. Subsequently, diethyl carbonate (5.75 mL, 47.3 mmol) was slowly added and stirring was continued for 30 minutes at -70°C. The reaction mixture was then warmed to room temperature and stirred for an additional 1 hour. Upon completion of the reaction, the reaction mixture was quenched with aqueous ammonium chloride and extracted with ethyl acetate. The organic layer was washed sequentially with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated to give the crude product. The crude product was purified by column chromatography on silica gel (100-200 mesh), using a petroleum ether solution of 9% ethyl acetate as eluent, to finally obtain ethyl 2-(6-chloropyridin-2-yl)acetate (2.21 g, 28% yield) as an oil.
