合成路线1

A similar method, but using a different protection strategy, has been reported. 4-Hydroxy-2,6-pyridinedicarboxylic acid (XVIII) was condensed with morpholine (II) to provide, after Fischer esterification, the morpholinopyridine diester (IV). Reduction of (IV) with calcium borohydride furnished hydroxy ester (V). Protection of (V) as the corresponding tetrahydropyranyl ether, followed by ester group saponification, afforded (XIX). Curtius rearrangement of acid (XIX) in the same conditions as above gave carbamate (XX), which was alkylated with benzyl chloride (XXI) yielding (XXII). After reduction of the nitroderivative (XXII) with iron and ammonium chloride, the resultant amine (XXIII) was acylated by allyl chloroformate to produce carbamate (XXIV). Then, acidic treatment removed the tetrahydropyranyl-protecting group to afford alcohol (XIV), which was finally processed as in the above method.