| 摘要 |
Prodn. of 5-fluoro-2-methyl-1-(p-methylsulphinyl-benzylidene)-indene-3-acet- ic acid (sulindac) (I), comprises (1) reacting 5-fluoro-2-methyl-1, 3-indanedione (II), in which the 3-keto group is opt. protected, with a p-methyl-sulphinylbenzylidene-tri(alkyl or aryl)-phosphorane (III) and condensing the resulting 5-fluoro-2-methyl-1-(p-methyl-sulphinylbenzylidene)-3-indanone (IV) with cyanoacetic acid; r (2) condensing (II) with cyanoacetic acid to give 5-fluoro-2-methyl-1-oxo-2-indene-3-acetic acid (V) and reacting (V), in which the COOH gp. may be protected by an ester residue, with (III).In an example, p-methylsulphinylbenzyl bromide is reacted with triphenylphosphine to give a phosphonium bromide which is treated with NaNH2 in liquid NH3 at -80 degrees. The resulting phosphorane is reacted with (II) 3-(ethylene ketal) to give (IV) ethylene ketal. Hydrolysis of this with aq. alcoholic HCl gives free (IV) which is reacted with cyanoacetic acid/acetic acid/ammonium acetate in refluxing toluene to give (I). |
