A mixture of methyl 2,6-dichloropyridine-4-carboxylate (2.00 g), dimethylzinc (2N toluene solution, 14.6 mL, 3.0 eq.), and PdCl2(dppf)2 (400 mg, 0.05 eq.) in dioxane (50 mL) was heated for 4 hr. at 80 °C under inert atmosphere. Upon completion of the reaction, the reaction mixture was cooled through an ice bath, quenched with water (100 mL) and filtered through a diatomaceous earth pad. The diatomaceous earth pad was rinsed with water and ethyl acetate (EtOAc). The filtrate was extracted with ethyl acetate (250 mL) and the organic layer was washed with brine (100 mL), dried over anhydrous magnesium sulfate (MgSO4) and concentrated. Purification by fast chromatography (methanol gradient in dichloromethane, 0 to 2%) afforded compound 99 (methyl 2,6-dimethylisonicotinate) as an orange oil in 96% yield.1H-NMR (400 MHz, DMSO): δ 2.51 (s, 6H, 2×CH3), 3.88 (s, 3H, O-CH3), 7.51 (s, 2H, Ar). Mass spectrum (M+H)+ m/z = 166.1.
