3,5-Pyridinedicarboxylic acid → Edaglitazone

Participants

Reaction Conditions

Reaction Steps

The content of the 1500 ml glass reactor was heated to 260° C. with a metal bath, while the content of the 1000 ml glass flask was heated to 145° C. The solution of 3,5-pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-, diethyl ester was transferred within 1 to 2 minutes to the stirred solution of 5-[[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]-benzo[b]thien-7-yl]methylene]-2,4-thiazolidinedione. The temperature dropped to 220-230° C. and the mixture was heated again to 260° C. After 10 to 15 minutes 5-[[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]benzo[b]thien-7-yl]methylene]-2,4-thiazolidinedione was completely converted, and the metal bath removed. When the reaction mixture reached a temperature of 90° C., 650 ml of a mixture of n-heptane and ethanol (9:1) was added via a dropping funnel within 10 minutes. The mixture was seeded with 5-{[4-[2-(5-methyl-2-phenyl-oxazol-4-yl)ethoxy]benzo[b]thiophen-7-yl]methyl}-2,4-thiazolidinedione and crystallization started at 50° C. The suspension was cooled to 0° C. and stirred at that temperature for 5 h. The crystals were filtered off and washed with 4 portions of ethanol each 125 ml. The wet material was dried at 140° C., 10 mbar for 15 h, which afforded 89.1 g of white crystalline 5-{[4-[2-(5-methyl-2-phenyl-oxazol-4-yl)ethoxy]benzo[b]thiophen-7-yl]methyl}-2,4-thiazolidinedione with a purity of 96.5% according to HPLC analysis, corresponding to a corrected yield of 92.5%.

Provenance & Evidence