To a cooled solution (−40 to −45° C.) of 2-bromo-5-methylpyridine 1-oxide (12 g, 63.8 mmol) in dry THF (250 mL) was added a solution of i-PrMgCl.LiCl (127 mL, 165.8 mmol, 1.3M) in THF and the reaction mixture was stirred for 1 hour at −40° C. Dry ZnCl2 (1 g, 127. mmol) was added and the reaction was warmed to room temperature and stirred for 1 hour. 2-Bromo-3-fluoro-6-methylpyridine (2 g, 127. mmol) and Pd(PPh3)4 (5. g, 4.4 mmol) were added and the reaction mixture was refluxed for 20 hours. The mixture was cooled 0° C. and stirred for 1 hour to afford a solid. The solid was collected by filtration and then dissolved in dichloromethane and washed with a saturated solution of ethylenediaminetetraacetic acid and saturated K2CO3 successively. The organic layers were separated, dried, and concentrated to give a residue which was purified by flash silica chromatography eluted with dichloromethane/MeOH (50:1) to give 2-(3-fluoro-6-methylpyridin-2-yl)-5-methylpyridine 1-oxide (4.3 g; 30.1%). 1HNMR (CDCL3): δ ppm 8.22 (s, 1H), 7.47-7.42 (m, 2H), 7.30-7.27 (m, 1H), 7.20-7.28 (m, 1H), 2.61 (s, 3H), 2.38 (s, 3H). MS [M+H] found 219.0.
