Hydrochloric Acid → tert-Butyl (6-chloro-5-fluoro-4-iodopyridin-3-yl)carbamate

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nBuLi (107 mL, 2.5 M in hexanes, 268 mmol) was added dropwise to a cooled (−78° C.) solution of (6-chloro-5-fluoro-pyridin-3-yl)-carbamic acid tert-butyl ester (22 g, 89.2 mmol) and N,N,N′,N′-tetramethylethylenediamine (40.5 mL, 268 mmol) in anhydrous diethyl ether (400 mL) under an argon atmosphere, ensuring that the internal temperature of the reaction was maintained below −60° C. On complete addition, the reaction mixture was allowed to warm to −20° C. and stirred for 90 minutes. The reaction mixture was cooled to −78° C. and a solution of iodine (70 g, 280 mmol) in THF (125 mL) was added dropwise over 15 minutes. The reaction mixture was allowed to gradually warm to ambient temperature and stirred overnight. The reaction mixture was poured onto 1M HCl (200 mL) and crushed ice (50 g) and the aqueous phase was extracted with ethyl ether (2×200 mL). The combined organic layer was washed with water (200 mL), aqueous potassium carbonate solution (150 mL), aqueous sodium thiosulfate solution (150 mL), and brine (150 mL), dried (Na2SO4), filtered and concentrated in-vacuo to afford a residue. The resultant residue was triturated with ethanol and the resultant solid was collected by filtration, washed with pentane and dried in-vacuo to afford the title compound as a white solid (27.2 g, 82%). The trituration liquors were concentrated and purified by flash chromatography (silica: toluene to 5% ethyl acetate/toluene) to afford an additional batch of the title compound as a white solid (4.0 g, 12%). Total yield=31.2 g, 94%. 1H NMR (400 MHz, CDCl3): 8.82 (s, 1H), 6.71 (s, 1H), 1.55 (s, 9H).

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