A new synthesis of tepoxalin has been described: The condensation of 4-chloroacetophenone (I) with succinic anhydride (II) by means of lithium bis(trimethylsilyl)amide in THF at -20 C gives 6-(4-chlorophenyl)-4,6-dioxohexanoic acid (III), which is cyclized with 4-methoxyphenylhydrazine (IV) by means of triethylamine in methanol at room temperature to afford 3-[5-(4-chlorophenyl)-1-(4-methoxyphenyl)pyrazol-3-yl]propanoic acid (V); finally this compound is condensed with methylhydroxylamine (VI) by means of oxalyl chloride and triethylamine at room temperature.
A new method for the synthesis of tepoxalin has been reported: The cyclization of 6-(4-chlorophenyl)-4,6-dioxohexanoic acid (I) with refluxing acetic anhydride gives 5-[2-(4-chlorophenyl)-2-oxoethylidene]tetrahydrofuran-2-one (II), which is treated with methylhydroxylamine to afford the corresponding N-hydroxy-N-methylamide (III). Finally, this compound is cyclized with 4-methoxyphenylhydroazine (IV) by means of Na2CO3 in refluxing ethanol.