PROCESS FOR PREPARING 2-THIO-2-SUBSTITUTED-ALKANOIC ACID DERIVATIVES

摘要

Anti-inflammatory agents such as salicylic acid, pyrazolone derivatives, indomethacin, etc. generally exhibit potent anti-inflammatory activity, but they also have serious side effects associated with them. The present invention provides a method of producing anti-inflammatory compounds not having as pronounced side effects. The compounds are 2-thio-2-substituted-alkanoic acid derivatives represented by the formula (I) (I) wherein A represents (1) a substituted-phenyl group of the formula in which y1 represents an isobutyl group or an unsubstitutedor substituted-phenoxy group wherein the substituent is a halogen atom, a trifluoromethyl group or an alkoxy group having 1 to 4 carbon atoms, or (2) a substituted-thienyl group of the formula in which y2 represents an alkyl group having 1 to 4 carbon atoms; R represents an alkyl group having 1 to 4 carbon atoms; R3 represents a phenyl group, an alkyl-phenyl group wherein the alkyl group has 1 to 4 carbon atoms, or an alkyl group having 1 to 4 carbon atoms; and R4 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms The process comprises reacting a 2-(arylthio or alkylthio)-2-substituted-acetic acid of the formula (III) (III) wherein A and R3 are as defined above, with an alkylating agent represented by the formula (II) RZ (II) wherein R is as defined above and Z represents a halogen atom , an alkyl- or arylsulfonyloxy group or a sulfuric acid ester residual group in the presence of at least 2 mols of a base per mole of the 2-(arylthio or alkylthio)-2-substituted-acetic acid, to form the compound of the formula (I) wherein R4 represents a hydrogen atom and, optionally, converting the resulting compound to the compound of the formula (I) wherein R4 represents an alkyl group by esterification.