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.

Alkylation of 2,4-di-tert-butyl-6-iodophenol (I) with bromopropane by means of NaH (1) or CsF (2) provides the corresponding propyl ether (II). Subsequent Suzuki coupling of aryl iodide (II) with 2-formylbenzeneboronic acid (III) leads to the biphenyl aldehyde (IV). This is then condensed with phosphonate (V) producing the dienoate ester (VI). Finally, the ethyl ester group of (VI) is hydrolyzed with LiOH to the target carboxylic acid (1,2).