Uses
(6-Hydroxy-1-benzofuran-3-yl)acetic Acid is a reactant in the synthesis of dihydrobenzofuran (6-{[4''-(2-ethoxyethoxy)-2'',6''-dimethylbiphenyl-3-yl]methoxy}-2,3-dihydro-1-benzofuran-3-yl)acetic acid as a potent and orally available GPR40/FFA1 agonist.
Synthesis
General procedure for the synthesis of 2-(6-hydroxybenzofuran-3-yl)acetic acid from 4-chloromethyl-7-hydroxychromen-2-one:
1. a mixture of 4-chloromethyl-7-hydroxychromen-2-one (21.0 g, 21.0 mmol) with 1 M aqueous sodium hydroxide solution (1 L) was stirred under reflux conditions for 2 hours.
2. After completion of the reaction, the reaction mixture was acidified with concentrated sulfuric acid.
3. The acidified mixture was extracted with ethyl acetate.
4. The extract was washed with saturated sodium chloride solution and dried over anhydrous sodium sulfate.
5. The dried organic phase was concentrated under pressure to give the intermediate (6-hydroxy-1-benzofuran-3-yl)acetic acid (18.0 g, 93.75% yield).
References
[1] Heterocycles, 1995, vol. 41, # 4, p. 647 - 650
[2] Patent: WO2012/11125, 2012, A1. Location in patent: Page/Page column 136-137
[3] Patent: WO2008/1931, 2008, A2. Location in patent: Page/Page column 87
[4] Journal of Medicinal Chemistry, 2012, vol. 55, # 4, p. 1538 - 1552
[5] Patent: CN104250239, 2016, B. Location in patent: Paragraph 0292; 0293; 0294
