To a de-gassed suspension of zinc powder (912 mg, 14 mmol) in DMA (2.3 mL) was added drop-wise a solution of chlorotrimethylsilane and 1,2-dibromoethane (0.1 mL, 7:5 v/v ratio) and the resultant mixture was stirred at room temperature for 15 minutes. To this mixture was then added dropwise to a solution of 3-iodoazetidine-1-carboxylic acid tert-butyl ester (3.2 g, 11.3 mmol) in DMA (8.0 mL) and the resultant mixture was stirred at room temperature for 15 minutes. In a separate flask, PdCl2(dppf)2.DCM (196 mg, 0.24 mmol) and then copper iodide (92 mg, 0.48 mmol) were added to a degassed solution of 2-chloro-4-iodopyridine in DMA (20 mL). After allowing to age for 30 minutes, the zinc suspension above was added to the iodopyridine solution and the reaction mixture was allowed to stir at room temperature for 2 hours. The resultant mixture was quenched by adding saturated ammonium chloride solution and was then extracted with TBME (×2). The combined organic washings were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (0-25% ethyl acetate in cyclohexane) to afford the title compound as a white solid (1.2 g, 56%). LCMS (Method F): RT=3.71 min, m/z: 414 [M+H+].
