Catalytic hydrogenation of 2-hydroxy-3-nitropyridine (I) in the presence of Pd/C affords 3-amino-2-hydroxypyridine (II). This is then acylated by 5-methylisoxazole-3-carbonyl chloride (III) to furnish the corresponding amide (IV). (1)
Deprotection of N-Boc-D-3,4-difluorophenylalanine (V) by means of HCl in dioxane yields aminoacid (VI). Subsequent diazotization of (VI) with NaNO2/H2SO4 leads to hydroxyacid (VII). After esterification of (VII) with methanolic HCl, the hydroxyester (VIII) is converted into triflate (IX) upon treatment with trifluoromethanesulfonic anhydride and 2,6-lutidine. Condensation of hydroxypyridine (IV) with triflate (IX) in the presence of NaH gives rise to the N-alkylated pyridone (X). The methyl ester group of (X) is then hydrolyzed to the corresponding carboxylic acid (XI) by means of either NaOH or LiI in pyridine. (1,2)
Treatment of the Boc-protected aminoalcohol (XII) with trifluoroacetic acid furnishes (XIII). This is then coupled with acid (XI) in the presence of HATU to afford the amide alcohol (XIV). Oxidation of (XIV) with the Dess-Martin periodinane (DMP) reagent gives rise to aldehyde (XV). Finally, Wittig condensation of aldehyde (XV) with isopropoxycarbonylmethylene triphenylphosphorane provides the target unsaturated ester. (1,2)