A new synthesis of the title compound, very similar to that already published, is reported: The condensation of 6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-1-benzopyran-2-ylmethyl methanesulfonate (I) with 2-(methylamino)ethanol (II) by heating at 120 C gives the tertiary amine (III), which is condensed with 4-fluorobenzaldehyde (IV) by means of NaH in DMF yielding the 4-alkoxy benzaldehyde (V). A new condensation of (V) with thiazolidine-2,4-dione (VI) by means of piperidine in refluxing toluene affords the benzyloxy derivative of the target compound (VII). Finally, the target compound is obtained by treatment of (VII) with HCl in acetic acid.

The condensation of 5-(benzyloxy)-2,2,4,6,7-pentamethyl-3,4-dihydrobenzofuran-3-ylmethyl methanesulfonate (I) with 2-(methylamino)ethanol (II) by heating at 120 C gives the tertiary amine (III), which is treated with SOCl2 in benzene yielding the chloroethylamino compound (IV). The condensation of (IV) with 4-nitrophenol (V) by means of K2CO3 in hot DMF affords the 4-nitrophenoxy compound (VI), which is reduced with H2 over Pd/C in ethyl acetate to the corresponding 4-aminophenoxy compound (VII). The condensation of (VII) with ethyl acrylate (VIII) by means of NaNO2 and HBr in methanol/water gives the 2-bromopropionic ester (IX), which is cyclized with thiourea (X) by means of NaOAc in refluxing ethanol yielding the thiazolidinedione (XI). Finally, this compound is debenzylated with HCl in hot acetic acid.

The condensation of the chloromethylamino intermediate (IV) with 5-(4-hydroxybenzyl)thiazolidine-2,4-dione (XII) by means of NaH in in hot DMF gives the previously reported intermediate (XI), which is finally deprotected with HCl in acetic acid as before.

Treatment of chromane (I) with metanesulfonyl chloride in pyridine at 0 C afforded mesylate (II), which was treated with 2-methylaminoethanol (III) to afford tertiary amine (IV). Reaction with SOCl2 gave chloride (V), and further reaction with p-hydroxybenzaldehyde (VI) provided (VII). Aldehyde (VII) was then condensed with 2,4-thiazolidinedione (VIII) in the presence of piperidine benzoate in toluene to furnish (IX). Finally, the benzyl protecting group was removed by treatment with acetic acid-hydrochloric acid at 60 C to give the title compound.