Floctafenine can be synthesized beginning with the conversion of ortho-trifluoromethyl aniline (1) to a
quinolol.[2][3][4] The compound is then
condensed with
ethoxy methylene malonic diethyl ester (EMME) and cyclized thermally (2). That intermediate is then
saponified; the resulting acid is
decarboxylated and finally converted to the 4-chloroquinoline (3) by reaction with
phosphorus oxychloride. The displacement of chlorine with
methyl anthranilate (4) then affords the coupled intermediate (5). An ester interchange of that product with
glycerol leads to the glyceryl ester, floctafenine (6).
^DE 1815467A1, Allais, André & Meier, Jean, "Neue Chinolidinderivate und Verfahren zu ihrer Herstellung [Novel quinolidine derivatives and processes for their preparation]", published 1969-07-24, assigned to
Roussel-Uclaf