Example 5: General procedure for the preparation of 2-methoxy-5-methylpyridine from 2-bromo-5-methylpyridine
1. 250 g (1.45 mol) of 2-bromo-5-methylpyridine, 2.1 g (1 mol%) of copper(I) bromide (CuBr), 14.5 g (2 mol%) of poly(ethylene glycol) dimethyl ether 500, and 457 g of 30% sodium methanol solution (precursor concentration of 14.5%) were added to a reactor.
2. the reaction mixture was heated to 90 °C and the progress of the reaction was monitored by GC until the conversion was >98.5% (reaction time totaled 17 hours).
3. upon completion of the reaction, the reaction mixture was quenched by slowly adding 750 g of water.
4. The pH of the mixture was adjusted to 9 by dropwise addition of hydrochloric acid, followed by filtration through decalite to remove insoluble material.
5. The aqueous phase was extracted twice with methyl tert-butyl ether (MTBE) (350 g each).
6. The organic phases were combined and subjected to vacuum fractionation to afford 162.8 g (1.32 mol, 91% yield) of 2-methoxy-5-methylpyridine with a GC purity of >98% (a/a).
