合成路线1

2) Synthesis of etoricoxib via ketosulfone (XXIV): a) The reaction of 6-methylpyridine-3-carboxylic acid methyl ester (XVIII) with N,O-dimethylhydroxylamine and isopropylmagnesium chloride in toluene gives the N-methoxyamide (XIX), which is reduced with DIBAL to afford 6-methylpyridine-3-carbaldehyde (XX). Reaction of aldehyde (XX) with aniline and diphenyl phosphite provides the diphenyl phosphonate (XXI), which is condensed with 4-(methylsulfonyl)benzaldehyde (XXII) by means of potassium tert-butoxide in HF to yield the enimine (XXIII). Finally, this compound is hydrolyzed with HCl to give ketosulfone (XXIV). b) Condensation of N-methoxyamide (XIX) with 4-(methylsulfanyl)benzylmagnesium bromide (XXV) in toluene/THF gives 1-(6-methylpyridin-3-yl)-2-[4-(methylsulfanyl)phenyl]ethanone (XXVI), which is finally oxidized with Na2WO4 to yield ketosulfone (XXIV). c) Oxidation of 4'-(methylsulfonyl)acetophenone (XXVII) with S8 and morpholine, followed by esterification with ethanol, affords 2-[4-(methylsulfonyl)phenyl]acetic acid ethyl ester (XXVIII); which is condensed with 6-methylpyridine-3-carboxylic acid methyl ester (XVIII) by means of t-BuMgCl in hot THF to furnish ketosulfone (XXIV).