Preparing aromatic carboxylic acid derivatives by nucleophilic aromatic substitution, comprises reacting carboxylic acid derivative having carboxyl function or its salts, preferably benzoic acid derivatives with metal compound

摘要

Preparing aromatic carboxylic acid derivatives by nucleophilic aromatic substitution, comprises: reacting an aromatic carboxylic acid derivative supporting only one carboxyl function, or one of its salts, preferably lithium, sodium, potassium or zinc salts, preferably benzoic acid derivatives or its salts with metal compound of formula (MNu) (III), where: the carboxylic acid derivative has, in ortho of carboxy function, a leaving group, which is a fluorine atom, chlorine atom or chiral or non chiral alkoxy group (preferably methoxy group). Preparing aromatic carboxylic acid derivatives by nucleophilic aromatic substitution, comprises: reacting an aromatic carboxylic acid derivative supporting only one carboxyl function, or one of its salts, preferably lithium, sodium, potassium or zinc salts, preferably benzoic acid derivatives or its salts with metal compound of formula (MNu) (III), where: the carboxylic acid derivative has, in ortho of carboxy function, a leaving group, which is a fluorine atom, chlorine atom or chiral or non chiral alkoxy group (preferably methoxy group); the carboxylic acid derivative is substituted by at least one electroattractive group other than the leaving group, preferably by a fluorine atom; if the leaving group is a fluorine atom, and the para position is occupied by a bromine atom and the other positions are substituted by hydrogen atoms, or (III) is not isobutyl magnesium chloride (iBuMgCl) or magnesium bromide of formula (N1uMgBr); if the leaving group is a fluorine atom, and the other ortho position is occupied by a halo, and the para position is occupied by a fluorine atom and the meta position adjacent to the leaving group and the other meta position is occupied by a hydrogen atom, and (III) is not an alkylating agent in which Nu is 1-6C alkyl; the starting product is 2,3,4,6-tetrafluorobenzoic acid and (III) is not methyl magnesium bromide (CH 3MgBr); the aromatic nucleophilic substitution reaction is carried out without catalyst and without protection/deprotection of the acid function of the starting compound; and the process is selective in that the reaction leads to the formation of ketone derivatives in a very minority manner during the reaction. M : metal; Nu : a chiral or non chiral nucleophile; and N1u : ethyl group, isobutyl group or cydopentenyl group.