First synthesis of methyl 2-amino-6-methoxynicotinate using a combination of microwave and flow reaction technologies
Jeges G., Meszaros T., Szommer T., Kovacs J., Nagy T., Tymoshenko D., Fotouhi N., Gillespie P., Kowalczyk A., Goodnow RA.
The synthesis of methyl 2-amino-6-methoxynicotinate, a valuable building block for the preparation of fused 2-pyridones, is reported. The optimized synthesis includes sequential microwave-induced regioselective 6-methoxylation, esterification, followed by microwave-induced reaction with p- methoxybenzylamine, and final deprotection under flow reaction hydrogenation conditions. Two key steps in the reported synthesis are a microwave-induced methoxylation and a microfluidic hydrogenation that afford improved regioselectivity and purity profile of the reaction products. © Georg Thieme Verlag Stuttgart.