Mesitylene → Edaglitazone

Participants

Reaction Conditions

Reaction Steps

A 2.5 l, 4-necked glass flask equipped with a mechanical stirrer, a thermometer, a cooler, a dropping funnel and an argon inlet was charged under argon in sequence with 118.2 g (250 mmol) of 5-[[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]benzo[b]thien-7-yl]methylene]-2,4-thiazolidinedione, 98.3 g (375 mmol) of 3,5-pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-, diethyl ester, 563 ml of mesitylene and 17.4 ml (125 mmol) of triethylamine. The suspension was stirred at reflux (ca. 167° C.) for 6 h, then the resulting solution was cooled to 90° C. within 50 min, finally 1560 ml of ethanol were added within 10 min whereas the temperature dropped to 40° C. The suspension was cooled to 0° C. and stirred at this temperature for 5 h. Finally the precipitate was isolated by filtration, the filter cake was washed with 700 ml of ethanol and dried over night at 60° C./10 mbar, to afford 101.1 g (92.3%) of 5-{[4-[2-(5-methyl-2-phenyl-oxazol-4-yl)ethoxy]benzo[b]thiophen-7-yl]methyl}-2,4-thiazolidinedione as off-white crystalline material with a m.p. of 208° C.

Provenance & Evidence