Fremgangsmåde til fremstilling af en 4-aryl-3-hydroksysmørsyre eller en ester eller et amid deraf.

摘要

The invention comprises (1) novel compounds of Formula I where X is hydroxy, alkoxy having up to 6 carbon atoms, or amino, R is hydrogen, halogen, trifluoromethyl, alkyl having up to 8 carbon atoms, a cycloalkyl or cycloalkenyl group having up to 7 carbon atoms an aryl group which may be substituted by halogen, methyl, ethyl, methoxy or ethoxy, analkoxy group having up to 8 carbon atoms, or an aryloxy group, and R1 is any of the atoms or groups described above for R, or R and R1 may together form a cyclic substituent and represent a methylenedioxy, cyclopenta or cyclohexa group, or the group may represent an a -naphthyl, b -naphthyl or phenanthyl radical, but when X is hydroxy, R and R1 cannot both be hydrogen, and pharmaceutically acceptable salts of the acid, and (2) the preparation of all compounds of Formula I above by converting a compound of formula where Hal represents halogeno, into the corresponding Grignard compound or lithium aryl, which is condensed with a 2,3-epoxypropyl halide, the corresponding 3-aryl-2-hydroxypropyl halide obtained being converted into the corresponding nitrile by treatment with an alkali metal cyanide in a solvent, and the nitrile being converted as required into the desired ester, acid, amide or salt. The nitrile may be converted to an ester by heating the nitrile in solution in an appropriate alkanol in the presence of an acidic catalyst. The ester may then be converted to the acid by warming with a slight excess of aqueous alkaline hydroxide solution. The acid may also be prepared by heating the nitrile with concentrated mineral acid. The amide is formed by warming the nitrile with hydrogen peroxide solution in the presence of an alkali. The resulting amide may be hydrolysed to the acid. Halophenylcycloalkenes may be prepared by treating the cycloalkanone with a halophenyl magnesium bromide and dehydrating the crude carbinol with acetic anhydride in acetic acid. 3-Bromo-4-butoxybiphenyl is prepared by treating the hydroxy compound with butyl bromide. Therapeutic compositions having anti-inflammatory activity and which may be administered e.g. orally, contain as active ingredient the novel compounds described above.