GENERAL STEPS: To a solution of 4-fluoroaniline (3.03 mL, 31.5 mmol, 1.0 eq.) in ethanol (30 mL) was added cyclic (sub)isopropyl malonate (Meldrum acid, 5.54 g, 38.4 mmol, 1.2 eq.) and triethyl orthoformate (12.4 mL, 74.5 mmol, 2.4 eq.), in that order. The reaction mixture was heated to reflux for 2.5 hours. Upon completion of the reaction, the mixture was cooled to 0 °C, the precipitated solid was collected by filtration and washed with cold ethanol. The dried solid was quickly added to boiling diphenyl ether (100 mL) and the reflux state was maintained for 3 minutes. Subsequently, the reaction mixture was stirred at room temperature for 30 min, petroleum ether (25 mL) was added to promote product precipitation, and the solid was collected by filtration and dried. The crude product was purified by silica gel column chromatography (eluent: EtOAc/MeOH, 95:5, v/v) to afford the target compound 6-fluoroquinolin-4-ol (2.36 g, 14.5 mmol, 46% yield). The product was analyzed (TLC, 1H NMR, 13C NMR, IR, LC-MS, HRMS and melting point determination) and confirmed to be consistent with the data reported in the literature. Ref: WO2010/123995 (2010).TLC Rf 0.41 (EtOAc/MeOH 95:5).1H NMR (400 MHz, DMSO-d6) δ (ppm): 11.90 (s, 1H, OH), 7.94 (d, J = 7.6 Hz, 1H, NCH), 7.73 (m, 1H, NCCH), 7.53 (m, 1H, NCCH). NCCH), 7.53-7.67 (m, 2H, FCCH), 6.04 (d, J = 7.3 Hz, 1H, OHCCH).13C NMR (101 MHz, DMSO-d6) δ (ppm): 159.9, 157.7, 140.0, 137.2, 127.3, 121.1, 120.8, 109.5, 108.3. 108.3. IR (neat) νmax: 2768 (br), 1594 (m) cm?1. LC-MS (ESI+) m/z: 164.1 [M + H]+, 186.1 [M + Na]+. HRMS (ESI+) m/z: Calculated value 164.0506, measured value 164.0509 [M + H]+. Melting point: 227-228 °C.
