Synthesis
General procedure for the synthesis of 4-hydroxy-7-(trifluoromethyl)quinoline-3-carboxylic acid from ethyl 4-hydroxy-7-(trifluoromethyl)quinoline-3-carboxylate: Compound I-D (5 g) and potassium hydroxide (3 equiv.) were dissolved in 60 ml of a solvent mixture of water and ethylene glycol (1:1) in a sealed XP-500 Plus container. The reaction was microwave heated at 200°C and 220-240 psi pressure for 30 minutes using a MARS 5 microwave system. After completion of the reaction, the mixture was cooled to room temperature and poured into 100 ml of water. The solution was acidified to pH ≈ 6 with 2N hydrochloric acid, subsequently saturated with sodium chloride and extracted with tetrahydrofuran (3 x 200 ml). The organic layers were combined, washed with brine and concentrated to give compounds I-E in over 80% yield.
References
[1] Patent: WO2005/63739, 2005, A1. Location in patent: Page/Page column 45-46
[2] Journal of Medicinal Chemistry, 1998, vol. 41, # 25, p. 4918 - 4926
[3] Journal of the American Chemical Society, 1947, vol. 69, p. 371,373
