Synthesis of methyl 5-methylpicolinate or methyl 5-methylpyridine-2-carboxylate

The post of today concerns a very beautiful synthesis of the pyridine ring, and more precisely of methyl pyridine-2-carboxylate. This synthesis has been described by Danheiser et al. and with a "imination" of the Meldrum's acid with sodium nitrite (NaNO2) followed by tosylation (TosCl). The tosylimine obtained has been engaged in aluminium catalyzed (Et2AlCl) Diels-Alder reaction with isoprene as diene (of course other dienes can be used, see reference), the bicyclic spiro compound has been treated by sodium methylate, N-chlorosuccinimide in a THF/MeOH mixture to give the desired methyl 5-methylpyridinecarboxylate.

Ref: Organic Syntheses, Vol. 80, p.133 (2003).