Methyl-3-bromo-4-methyl-5-nitropicolinate synthesis: 3-bromo-2-iodo-4-methyl-5-nitropyridine (129.0 g, 0.38 mol) and (Ph3P)2PdCl2 (7.92 g, 3 mol%) were suspended in CH3CN (1300 mL) and MeOH (430 mL) and Et3N (79.3 mL, 1.5 eq) was added. The mixture was transferred to a steel 5000 mL pressure vessel, 4 bar of CO pressure was applied and the reaction mixture was slowly heated to 80 oC. Subsequently, it was stirred for 5 h at this temperature, then allowed to cool overnight. The volatiles were removed in vacuo, the residue was stirred in EtOAc (1000 mL) and filtered. The residue was extracted with EtOAc (2*250 mL) and the combined filtrates were washed with brine (1000 mL) and dried on Na2SO4. The volatiles were removed in vacuo, affording 120 g of a brown oil. This was coated on 120 g of silicagel and purified by column chromatography (3500 g of silica gel, EtOAc/heptane 1:3, KMnO4 staining). The appropriate fractions were combined and concentrated to give Methyl-3-bromo-4-methyl-5-nitropicolinate as a beige solid (63.5 g, 61%).
