合成路线1

Addition of methyllithium to 3,5-di-tert-butylsalicylic acid (I) affords ketone (II). Wittig condensation of the ortho-hydroxyacetophenone (II) with (carbethoxymethylene)triphenylphosphorane leads to the coumarin derivative (III). Subsequent reductive opening of the lactone ring of (III) by means of LiAlH4 provides diol (IV). The phenolic hydroxyl of (IV) is then alkylated by 1,1-difluoro-2-bromoethane (V) in the presence of CsF to furnish the difluoroethyl ether (VI). Oxidation of the allylic alcohol function of (VI) to aldehyde (VII) is accomplished by treatment with tetrapropylammonium perruthenate and N-methylmorpholine-N-oxide. Wadsworth-Emmons condensation of the unsaturated aldehyde (VII) with phosphonate (VIII) then provides the triene adduct (IX). The ethyl ester group of (IX) is finally hydrolyzed under alkaline conditions to the desired carboxylic acid.