合成路线1

The intermediate 4-(4-methoxyphenyl)-2-methylpyridine (IV) was obtained by two different procedures. Acylation of 2-picoline (I) with ethyl chloroformate, followed by addition of the Grignard reagent (II), prepared from 4-bromoanisole and magnesium, furnished the 4-aryl dihydropyridine (III). Aromatization of (III) by heating at 200 C with sulfur in decahydronaphthalene produced the phenylpyridine (IV). In an alternative method, 2-methylpyridine (I) was converted to the N-aminopyridinium salt (V) by reaction with hydroxylamine-O-sulfonic acid. This was then condensed with dehydroacetic acid (VI) under acidic conditions to produce the bipyridinium derivative (VII), which was isolated as the tetrafluoroborate salt. Alternatively, addition of 4-methoxyphenylmagnesium bromide (II) to (VII) yielded the phenyl bipyridinone (VIII), which upon elimination of the dimethylpyridone moiety in refluxing DMF generated the intermediate phenyl pyridine (IV). Methyl ether cleavage of (IV) in refluxing HBr afforded phenol (IX). This was then alkylated with 3-chloro-3-methylbutyne (X) to yield the aryl propargyl ether (XI) ,which was subjected to a Claisen rearrangement in hot ortho-dichlorobenzene to produce chromene (XII).