Reaction Steps
To a solution of compound 3 (1.65 g, 6.29 mmol) in anhydrous tetrahydrofuran (THF, 80 mL) were successively added, under argon, 2-fluoro-3-hydroxypyridine (0.72 g, 6.37 mmol) (Dollé, F.; Valette, H.; Bottlaender, M.; Hinnen, F.; Vaufrey, F.; Guenther, I.; Crouzel, C. Synthesis of 2-[18F]fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine, a highly potent radioligand for in vivo imaging central nicotinic acetylcholine receptors. J. Label. Compds. Radiopharm. 1998, 41, 451-463), triphenylphosphine (1.65 g, 6.29 mmol) and dropwise diisopropyl azodicarboxylate (DIAD, 1.71 mL, 8.68 mmol). The mixture was stirred at room temperature for 24 h. The solvent was evaporated under reduced pressure and the residue was chromatographed (Al2O3, AcOEt) to give compound 4 (1.77 g, 4.95 mmol) as a yellow solid. Yield 79%; Rf (Al2O3, AcOEt) 0.84; mp 58-60° C.; IR (KBr) ν 1192, 1240, 1290, 1395, 1452, 1712, 2847, 2943 cm−1; 1H NMR (200 MHz, CDCl3) δ 1.29 (t, 3H, J=7.1 Hz), 2.97 (q, 2H, J=7.1 Hz), 3.14 (t, 2H, J=6.5 Hz), 3.24 (t, 2H, J=5.9 Hz), 4.08 (t, 2H, J=6.5 Hz), 4.31 (t, 2H, J=5.9 Hz), 7.35 (ddd, 1H, 5JH-F=0.9 Hz, J=4.8, 7.8 Hz), 7.52 (ddd, 1H, 4JH-F=10.0 Hz, J=1.6, 7.8 Hz), 7.97 (m, 3H), 8.07 (m, 2H); MS m/z 357 (M+, 1), 231 (15), 197 (100), 174 (23), 130 (10), 85 (17), 76 (10), 57 (45).
