Triethylamine → Edaglitazone

Participants

Reaction Steps

A 35 ml stainless steel autoclave equipped with a magnetic stirring bar was charged under argon with 1.18 g (2.5 mmol) of 5-[[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]-benzo[b]thien-7-yl]methylene]-2,4-thiazolidinedione, 0.985 g (3.75 mmol) of 3,5-pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-diethyl ester, 3.56 g of Dowtherm A and 0.18 ml (1.25 mmol) of triethylamine. The autoclave was closed and immersed into an oil bath at 230° C. The reaction was run with stirring (800 rpm) for 20 min, then the autoclave was cooled in water to room temperature, opened and a sample was taken from the clear, yellowish solution for HPLC analysis (conversion was 99.8%). The reaction mixture was transferred into a 50 ml round flask and the autoclave was rinsed with a total of 16 ml of ethanol. Immediately after the ethanol was added, crystals started to form. The yellowish suspension was stirred for 1 h at room temperature and in an ice bath (ca. 2° C.) for 4 h. The precipitate was filtered with suction, the filter cake was washed with a total of 7 ml of ethanol and dried (60° C., 25 mbar, 17 h) to afford 0.94 g (77.3%) of 5-{[4-[2-(5-methyl-2-phenyl-oxazol-4-yl)ethoxy]benzo[b]thiophen-7-yl]methyl}-2,4-thiazolidinedione as a yellowish solid, which according to quantitative HPLC analysis (column: XTerra TM RP18, 3.5 mm, Waters Art. 186000442, mob. phase pH 4.5 buffer/acetonitrile with gradient, flow 1 ml/min, UV detection, retention time of starting material 16.3 min, retention time of product 12.5 min) was 95.5% pure.

Provenance & Evidence