[Synthesis]
Example 1 Synthesis of 2-fluoro-4-iodo-3-(hydroxymethyl)pyridine: A solution of LDA was prepared by reacting diisopropylamine (0.63 mL, 4.49 mmol) with n-butyllithium (4.49 mmol) in tetrahydrofuran (THF, 10 mL) at -78 °C and under nitrogen protection. To this solution, a solution of 2-fluoro-3-iodopyridine (1 g, 4.48 mmol) dissolved in THF (2 mL) was added dropwise and stirred for 1 hour at -78 °C. Subsequently, ethyl formate (1.1 mL, 13.6 mmol) was added at the same temperature and stirring was continued for 30 min. The reaction mixture was quenched with saturated sodium bicarbonate solution and slowly warmed to room temperature. Sodium borohydride (0.34 g, 8.99 mmol) was slowly added to the mixture and stirred for 30 minutes before extracting with ethyl acetate. The organic phases were combined, washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by radial preparative thin layer chromatography (silica gel, hexanes, 10% ethyl acetate/hexanes, 20% ethyl acetate/hexanes) to give 708 mg (62% yield) of the target product as a white solid with a melting point of 69°-70 °C. Elemental analysis (C6H5FINO): calculated values: C 28.48, H 1.99, N 5.54; measured values: C 28.55, H 1.94, N 5.48. IR spectrum (KBr, cm^-1): 3336, 1584, 1541, 1446, 1401, 1264, 1218, 1003, 870, 833, 803. 761, 577. 1H NMR (CDCl3): δ 7.79-7.82 (d, 1H, J = 5 Hz), 7.66-7.68 (d, 1H, J = 5 Hz), 4.82-4.86 (d, 2H, J = 7 Hz), 1.99-2.04 (t, 1H, J = 14 Hz). 13C NMR (CDCl3): δ 162.29, 159.05, 147.30, 147.09, 132.79, 132.73, 126.14, 125.73, 114.21, 62.24. |