Synthesis
The general procedure for the synthesis of 4-isoquinolinecarboxylic acid from 4-cyanoisoquinoline was as follows: potassium hydroxide (20 g, dissolved in 20 mL of water) was added to a stirred solution of 4-cyanoisoquinoline (3.0 g, 19.45 mmol) in ethanol (30 mL) and the reaction mixture was refluxed overnight. Upon completion of the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure to remove the ethanol. Subsequently, the residue was washed with water and the aqueous layer was extracted with ether (Et2O). The aqueous layer was neutralized with 1N hydrochloric acid and extracted with ethyl acetate (EtOAc). The organic layers were combined, dried with anhydrous sodium sulfate (Na2SO4), filtered, and concentrated under reduced pressure to give 4-isoquinolinecarboxylic acid (2 g, 59.3% yield) as an off-white solid.
References
[1] Patent: US2013/178457, 2013, A1. Location in patent: Paragraph 0221
[2] Patent: WO2013/5168, 2013, A2. Location in patent: Page/Page column 40
[3] Journal of the American Chemical Society, 1940, vol. 62, p. 3030
[4] Journal of the American Chemical Society, 1939, vol. 61, p. 183
[5] Archiv der Pharmazie, 2003, vol. 336, # 4-5, p. 258 - 263
