Hydrochloric Acid → Rivoglitazone

Participants

Reaction Steps

A reaction mixture of 5-methoxy-N-methyl-1,2-phenylenediamine (21.8 g) (see Reference example 9 of Japanese Patent Application Publication No. Hei 9-295970), 5-(4-methoxycarbonylmethoxybenzyl)thiazolidine-2,4-dione (63.4 g) (see Reference example 21 of Japanese Patent Application Publication No. Hei 9-295970), 1,4-dioxane (250 ml) and concentrated hydrochloric acid (750 ml) was heated under reflux for 60 hours. The reaction mixture was cooled in an ice bath, and the resulting precipitate was filtered off. To this precipitate was added 5% aqueous sodium hydrogencarbonate solution (800 ml), and the mixture was stirred at room temperature for 2 hours. The precipitate was filtered off, dissolved in a mixed solvent of N,N-dimethylformamide (1000 ml) and methanol (200 ml), and then the solution was decolorized with activated charcoal powder. After the activated charcoal powder was filtered out, the solution was concentrated to a volume of about 50 ml. Diethyl ether (750 ml) was added thereto and the resulting solution was allowed to stand for 2 days to give a precipitate, which was filtered off to afford the target compound (20.1 g, mp 267–271° C., Rf-value=0.68 (silica gel chromatography; 5% ethanol-methylene chloride solution)).

Provenance & Evidence