Synthesis
General procedure for the synthesis of 8-hydroxyquinoline-6-carboxylic acid from 4-amino-3-hydroxybenzoic acid and acrolein [stabilized]: acrolein (21.8 mL, 326 mmol) was added slowly and dropwise to an aqueous 12 N solution (50 mL) containing 4-amino-3-hydroxybenzoic acid (5.00 g, 33.0 mmol). The reaction mixture was heated to reflux for 1 hour. Upon completion of the reaction, the mixture was cooled to room temperature and subsequently concentrated under reduced pressure to remove the solvent. The resulting residue was purified by reversed-phase chromatography (elution gradient: water:CH3CN 100:0 to 50:50), resulting in the target product 8-hydroxyquinoline-6-carboxylic acid (561 mg, 9% yield). The product was analyzed by UPLC/MS (ES+) and showed m/z 190.04 [M+H]+.
References
[1] Journal of Medicinal Chemistry, 2013, vol. 56, # 2, p. 521 - 533
[2] Patent: WO2015/26792, 2015, A1. Location in patent: Paragraph 0421
