General procedure for the synthesis of methyl 2-chloro-5-methylnicotinate from methylboronic acid and methyl 5-bromo-2-chloronicotinate: To a toluene solution (16 mL) of methyl 5-bromo-2-chloronicotinate (1.05 g, 4.19 mmol), K3PO4 (2.95 g, 13.90 mmol), methylboronic acid (0.32 g, 5.26 mmol) and tricyclohexylphosphine (0.11 g, 0.39 mmol) in a toluene solution (16 mL) under nitrogen atmosphere, water (0.8 mL) was added followed by Pd(OAc)2 (0.04 g, 0.18 mmol). The mixture was heated at 100 °C under nitrogen atmosphere for overnight reaction. After completion of the reaction, the mixture was cooled to room temperature and concentrated under vacuum. Ethyl acetate was added to the residue and the organic layer was washed sequentially with water and brine, dried with MgSO4, filtered and the solvent was evaporated under vacuum to afford the target product methyl 2-chloro-5-methylnicotinate as a yellow oil in 87% yield.LRMS: m/z 186 (M + 1)+, retention time: 4.84 min.
