Synthesis
The general procedure for the synthesis of 6-quinolineacetic acid from p-aminophenylacetic acid (20 g, 0.132 mol) and glycerol (51 g, 0.555 mol) is as follows: aminophenylacetic acid, FeSO4 (4.9 g, 0.032 mol), glycerol, PhNO2 (10.5 g, 0.086 mol) and concentrated H2SO4 (23 mL) were mixed, heated to 200°C and maintained for 5 hours. Upon completion of the reaction, the pH of the reaction mixture was adjusted to 10 with 4N NaOH aqueous solution. the reaction mixture was filtered and the clarified filtrate was acidified with AcOH to pH ca. 5. The resulting precipitate was collected by filtration to afford 6-quinolineacetic acid (12.5 g, 51% yield) as a brown solid. tLC conditions: 20% MeOH/CH2Cl2, Rf=0.2. 1H NMR ( 300MHz, DMSO-d6) δ ppm: 8.85 (m, 1H), 8.31-8.28 (m, 1H), 7.96 (d, J=8.3Hz, 1H), 7.82 (m, 1H), 7.67-7.64 (m, 1H), 7.50-7.49 (m, 1H), 3.78 (s, 2H).
References
[1] Patent: WO2013/19682, 2013, A1. Location in patent: Page/Page column 117
[2] Journal of Medicinal Chemistry, 2013, vol. 56, # 17, p. 6651 - 6665
[3] Patent: WO2007/138472, 2007, A2. Location in patent: Page/Page column 28
[4] Journal of the American Chemical Society, 1948, vol. 70, p. 2843,2945
[5] Patent: WO2009/137404, 2009, A1. Location in patent: Page/Page column 60
