Synthesis
GENERAL METHODS: Polyphosphoric acid (PPA) (2 eq. by weight) was mixed with Intermediate 1 (40 mmol), followed by the addition of phosphoryl chloride (POCl3) (10 mmol). The reaction mixture was heated to 75 °C and maintained for 8 h. The reaction progress was monitored by thin layer chromatography (TLC). Upon completion of the reaction, the mixture was quenched by slowly pouring it into 10% sodium hydroxide solution in an ice bath while adjusting the pH to about 7. The resulting solid was separated by filtration, dried, and washed with ether (3 x 20 mL) to afford ethyl 4-hydroxy-6-trifluoromethylquinoline-3-carboxylate in good yield.
References
[1] European Journal of Medicinal Chemistry, 2015, vol. 103, p. 1 - 16
[2] Organic Process Research and Development, 2014, vol. 18, # 11, p. 1482 - 1491
[3] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 6, p. 1577 - 1580
