Iodine → 6-Chloro-4-iodo-2-(ethoxymethoxy)-3-hydroxymethylpyridine

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To a solution of 2.5M n-butyllithium (2.2 mL, 5 mmol) in 20 mL of THF at -10° C. was added 0.94 g 2-chloro-6-(ethoxymethoxy)pyridine (5 mmol) dropwise over 2 min. The reaction mixture was stirred for 10 min. at -10° C., then cooled to -23° C. and 0.72% N-formyl-N,N',N'-trimethylethylenediamine) was added. After stirring at -23° C. for 30 min., n-butyllithium (2.5M, 3 mL, 7.5 mmol) was added dropwise and the dark reaction mixture was stirred at -23° C. for 4 hr. The mixture was transferred via a double-tipped meedle to a solution of 1.9 g of iodine (7.5 mmol) in 10 mL of DME and 10 mL of THF at -78° C. After stirring at -78° C. for 30 min., the cooling bath was removed. 0.3 g of solid sodium borohydride (8 mmol) was added to the red mixture. 10 mL of water was added dropwise with vigorous stirring. After 30 min., the mixture was extracted with three 20 -mL portions of EtOAc. The combined organic layers were washed with 20 mL of 10 percent sodium thiosulfate solution, water and brine. After drying over sodium carbonate, the solvents were removed under reduced pressure to yield the 1.3 g of crude product, which was purified by radial PLC (10% EtOAc/hexane) to give 0.7 g (40%) of pure product as a white solid, mp 43°-44° C. 1H NMR (300 MHz, CDCl3) δ 7.43 (s, 1 H), 5.62 (s, 2 H), 4.79 (s, 2 H), 3.78 (q, 2 H, J=7.1 Hz), 2.24 (brd, 1 H), 1.26 (t, 3 H, J=7.1 Hz). 13C NMR (75 MHz, CDCl3) δ 158.9, 147.8, 127.3, 124.7, 113.5, 92.0, 66.0, 63.2, 15.0. Analysis Calculated for C9H11ClNO3 : C, 31.47; H, 3.23; N, 4.08. Found: C, 31.68; H, 3.28; N, 4.13.

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