Reaction of aldehyde (III) with 2-fluorobenzyl alcohol (VIII) by means of triphenylphosphine and diethyl azodicarboxylate (DEAD) in THF furnishes 6-(2-fluorobenzyloxy)naphthalene-2-carbaldehyde (IX) , which is then reduced with NaBH4 in ethanol/THF to give the naphthalenemethanol derivative (X). Halogenation of (X) by means of iodide, triphenylphosphine and imidazole in THF yields the naphthylmethyl iodide derivative (XI), which is finally condensed with thiazolidine-2,4-dione (IV) by means of HMPA and butyl lithium in THF.
Reduction of 6-hydroxynaphthalen-2-carboxylic acid (I) by means of trimethyl borate and BH3.THF complex ?obtained by reaction of NaBH4 and dimethyl sulfate in THF ?yields the naphthyl carbinol derivative (II), which is oxidized to aldehyde (III) with either manganese dioxide in DMF or acetone, mixtures of CuCl2, CuBr2 or FeCl3 with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) in DMF or O2, TEMPO and a ruthenium catalyst in chlorobenzene. Condensation of aldehyde (III) with thiazolidine-2,4-dione (IV) in 2-methoxyethanol, 2-propanol, DMF or DMSO gives 5-(6-hydroxynaphthalen-2-ylmethylene)thiazolidine-2,4-dione (V), which is then reduced with either H2 over catalyst or cyclohexene to provide 5-(6-hydroxynaphthalen-2-ylmethyl)thiazolidine-2,4-dione (VI). Finally, compound (VI) is condensed with 2-fluorobenzyl chloride (VII) by means of NaH or KH in DMF, DMSO or NMP.