Step A: Preparation of 2-chloromethyl-6-fluoropyridine
To a solution of 2-fluoro-6-methylpyridine (0.23 mL, 2.2 mmol) in acetonitrile (5 mL) was sequentially added N-chlorosuccinimide (440 mg, 3.3 mmol), benzoyl peroxide (14 mg, 0.044 mmol) and glacial acetic acid (10 μL). The reaction mixture was heated at 85 °C with stirring for 4 h, followed by continued stirring for 18 h at room temperature. Upon completion of the reaction, the mixture was partitioned between ethyl acetate and water. The organic phase was washed sequentially with water and saturated saline and dried over anhydrous magnesium sulfate. The desiccant was removed by filtration and the filtrate was concentrated under reduced pressure to give the crude product. Purification of the crude product by normal phase column chromatography (eluent: ethyl acetate/heptane) afforded 2-chloromethyl-6-fluoropyridine as a colorless oil (240 mg, 75% yield).
