2-Hydroxyquinoline → 3,4,6-trichlorophthalic Acid

Participants

Reaction Steps

2,4,5-Trifluorobenzoic acid (2,4,5--TiFBA) is used as an intermediate in preparing quinolone antibacterials. It is prepared by a process that begins with tetrachlorophthalic anhydride. Tetrachlorophthalic anhydride is first hydrodechlorinated in NaOH/Zn to produce 3,4,6-trichlorophthalic acid, followed by imidization using methylamine to form 3,4,6-trichloro-N-methylphthalimide. That product is fluorinated by KF to form 3,4,6-trifluoro-N-methyl phthalimide, which is hydrolyzed to produce 3,4,6-trifluorophthalic acid. Decarboxylation results in a solution of 2,4,5-TiFBA in an organic decarboxylating solvent such as N-methylpyrrolidone (NMP).

Provenance & Evidence