6-FLUORO-4-HYDROXYQUINOLINE

To a solution of p-fluoroaniline (3.03 mL, 31.5 mmol, 1 equiv) in ethanol (30 mL) were added Meldrum's acid (5.54 g, 38.4 mmol, 1.2 equiv) and triethyl orthoformate (12.4 mL, 74.5 mmol, 2.4 equiv). The mixture was heated to reflux for 2.5 h. The reaction was cooled to 0 °C and the solid was filtered and washed with cold ethanol. The dried solid was added portiowise over 5 mins to boiling diphenyl ether (100 mL). Reflux was maintained for an additional 3 mins. The reaction was stirred at room temperature for 30 mins before petroleum ether (25 mL) was added and the solid was filtered and dried. The crude product was purified by column chromatography on silica gel (EtOAc/MeOH 95:5), to afford 6-fluoroquinolin-4-ol (2.36 g, 14.5 mmol, 46percent). The analyses were consistent with the data reported in the literature. Ref: WO2010/123995 (2010) TLC RGeneral procedure: To a screw-capped test tube equipped with a magnetic stir bar was added 1a (0.2 mmol, 1.0 eq.) and t-BuONa (38.4 mg, 0.4 mmol, 2.0 equiv.). Then, air was withdrawn and backfilled with N2 (three times). Perfluorobutyl iodide 2a (103.8 mg, 0.3 mmol, 1.5 equiv.) and DMF (2.0 mL) was added by syringe. Thereafter, the test tube was stirred under green LED (15 W) irradiation at room temperature. After 90 min, the resulting mixture was diluted with HCl (1 mol/L) and extracted with EtOAc (10 mL×3). The organic layer was washed with brine and dried over MgSO4, concentrated in vacuo and purified by column chromatography (1:1 hexane/EtOAc) to afford the desired product 3a.