合成路线1

The reaction of ethyl 2-methylacetoacetate (X) with NH3 in ethanol in an autoclave at 80 C gives ethyl 3-amino-2-methylcrotonate (XI), which is cyclized with diethyl 2-methylmalonate (XII) yielding 2,4-dihydroxy-3,5,6-trimethylpyridine (XIII). The reaction of (XIII) with POCl3 at 150 C affords 2,4-dichloro-3,5,6-trimethylpyridine (XIV), which is partially dechlorinated with H2 over Pd/C in ethanol/H2SO4 giving 4-chloro-2,3,5-trimethylpyridine (XV). The reaction of (XV) with sodium methoxide in hot DMSO yields 4-methoxy-2,3,5-trimethylpyridine (XVI), which is oxidized with H2O2 in AcOH affording the corresponding N-oxide (XVIII). The reaction of (XVIII) with acetic anhydride in hot acetic acid provides the acetate ester (XIX), which is finally hydrolyzed in the usual way to the target intermediate the 4-methoxy-3,5-dimethylpyridine-2-methanol (VI). The intermediate 4-chloro-2,3,5-trimethylpyridine (XV), can be oxidized with H2O2 in AcOH as before to give the corresponding N-oxide (XVII), which is treated with sodium methoxide in DMSO/methanol affording the previously described 4-methoxy-2,3,5-trimethylpyridine N-oxide (XVIII).