Iodine → 1,1-Dimethylethyl N-[4-iodo-6-(1-methylethoxy)-3-pyridinyl]carbamate

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Reaction Steps

A solution of 13.7 g of 5-[(tert-butoxycarbonyl)amino]-2-(isopropoxy)pyridine (54.3 mmol) and 18.1 mL of N,N,N′-tetramethylethylenediamine (120 mmol) in 200 mL of anhydrous diethyl ether was cooled to −78° C. and treated with n-BuLi (2.5 M in hexanes, 48 mL, 120 mmol) under an inert atmosphere. The mixture was placed in a −8° C. bath for 1 hour and allowed to slowly warm to room temperature. After 40 minutes, the flask was cooled to −8° C. and stirred for 4 hours. The mixture was then cooled to −78° C., treated with a solution of iodine (19.0 g, 75 mmol) in 100 mL of anhydrous THF, and the resulting mixture was stirred for 16 hours while allowing the bath to warm to 11° C. The reaction mixture was poured into a rapidly stirring aqueous saturated ammonium chloride solution (200 mL) and diluted with 100 mL of water and 300 mL of diethyl ether. The phases were separated and the aqueous layer was extracted with 200 mL of diethyl ether. The combined organic layers were washed with two 200 mL portions of sodium thiosulfate (10% aqueous solution), dried over sodium sulfate, decanted, and concentrated in vacuo. Chromatography on SiO2 (10% to 50% ethyl acetate in hexanes, gradient) gave the title product as an oil, which solidified on standing (13 g, 63% yield).

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