• Archives of Pharmacal Research
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• v.15 no.2
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• pp.142-145
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• 1992

A novel preparative method for hexaprofen, which is a potent antiinflammatory agent, is described. Friedel-Crafts reaction of cyclohexylbenzene with ethyl $\alpha$-chloro-$\alpha$-(methylthio) acetate 1 and $\alpha$-chloro-$\alpha$-(methylthio) acetonitrile 2 afforded ethyl 2-(methylthio)-2-(4-cyclohexylphenyl) acetate 7 and 2-methylthio-2-(4-cyclohexylphenyl) acetonitrile 8, respectively. Compounds 7 and 8 were converted into the corresponding ethyl 2-methylthio-2-(4-cyclohexylphenyl) propionate 9 and 2-methylthio-2-(4-cyclohexylphenyl) propionitrile 10 by methylation with sodium hydride and methyl iodide. Hexaprofen 13 was prepard by hydrolysis of ethyl 2-(4-cyclohexylphenyl) propionate 11 and of 2-(4-cyclohexylphenyl) propionitrile 12 followed by desulfurization of compounds 9 and 10.