Demethylation of methyl 4-(4-methoxyphenyl)butyrate (I) using boron tribromide affords phenol (II). Subsequent alkylation of (II) with t-butyl 2-bromoisobutyrate (III) yields ether (IV). The methyl ester group of (IV) is then selectively displaced with hydrazine hydrate to form hydrazide (V). This is condensed with p-methylbenzaldehyde (VI) to give hydrazone (VII), which is further reduced to (VIII) by catalytic hydrogenation over PtO2. Reaction of acyl hydrazide (VIII) with trimethylsilyl isocyanate leads to the acyl semicarbazide (IX). Finally, simultaneous t-butyl ester cleavage and cyclization to the target triazolone is accomplished by treatment of (IX) with several different sulfonic acids.
In an alternative method, 4-(4-methoxyphenyl)butyric acid (I) is demethylated to phenol (II) by heating at 190 C with pyridine hydrochloride. Alkylation of phenol (II) with ethyl 2-bromoisobutyrate (III) gives ether (IV). The carboxyl group of (IV) is then activated as the corresponding acid chloride (V) by treatment with oxalyl chloride in the presence of DMF.
Reductive alkylation of tert-butyl carbazate (VI) with 4-methylbenzaldehyde (VII) under catalytic hydrogenation conditions affords the N-p-methylbenzyl carbazate (VIII). This is then condensed with trimethylsilyl isocyanate to form the semicarbazide derivative (IX). Subsequent acidic Boc group cleavage in (IX) yields (X). Semicarbazide (X) is then acylated with acid chloride (V) producing (XI). Cyclization of the acyl semicarbazide (XI) in the presence of CSA leads to triazolone (XII). Finally, alkaline hydrolysis of the ethyl ester group of (XII) furnishes the title carboxylic acid.