The synthesis of
parecoxib sodium (19) started from commercially available
deoxybenzoin (165). Deoxybenzoin (165) was treated with
hydroxylamine in EtOH/H2O (3:1) to give deoxybenzoin
oxime 166 in 95% yield. Deprotonation of oxime 166 with
two equivalents of n-hexyllithium followed by condensation
with ethyl acetate afforded isoxazoline 167 in 59% yield.
Treatment of isoxazoline 167 with chlorosulfonic acid
followed by reaction of the incipient sulfonyl chloride with
aqueous ammonia furnished valdecoxib (27). Acylation of
isoxazole sulfonamide 27 with propionic anhydride afforded
parecoxib, which was converted to its sodium salt by
titration with aqueous sodium hydroxide (64%).
