(+/-)-2-[p-(1-Oxo-2-isoindolinyl)phenyl]butyric acid (인도부펜)의 합성

Facile Synthesis of (+/-)-2-[p-(1-Oxo-2-isoindolinyl)phenyl]butyric acid (Indobufen)

A convenient method for the synthesis of indobufen, which is a potent antiinflammatory agent, was described. Ethyl 2-phenylbutyrate(4) was prepared by Friedel-Crafts reaction of benzene with ethyl alpha-chloro-alpha-(methylthio)acetate(l) followed by ethylation and desulfurization of the resultant ethyl 2-(methylthio)phenylacetate(2). Ethyl 2-(p-aminophenyl)butyrate(6) was prepared by nitration of (4) and successive reduction of ethyl 2-(p-nitrophenyl) butyrate(5). Indobufen was obtained by condensation reaction of (6) with phthalic anhydride followed by reduction and hydrolysis of the resultant ethyl 2-[p-(1,3-dioxo-2-isoindolinyl)phenyl]butyrate(7).