Hydrochloric Acid → Ethyl 6-(4-fluorophenoxy)nicotinate

Participants

Reaction Conditions

Reaction Steps

Sodium hydride (0.653 g, 60% in mineral oil, 16.338 mmol) was suspended in DMF (10 mL) under argon, and 4-fluorophenol (0.915 g, 8.169 mmol) added in two portions. The mixture was stirred for 20 minutes then ethyl 6-chloro-3-pyridinecarboxylate (1.515 g, 8.169 mmol) was added together with additional DMF (4 mL) added to aid solubility. The mixture was heated to 80° C. for 2.5 h. The reaction mixture was allowed to cool to room temperature and water (30 mL) was added. The solution was acidified to pH 3 with 2M HCl and extracted with ethyl acetate (×3). The combined ethyl acetate layers were dried and concentrated to produce a brown oil. The crude product was purified by chromatography. Elution with a 0-25% Et2O/petroleum ether gradient gave the title compound as a colourless oil (0.284 g). δH (CDCl3, 400 MHz) 8.81 (1H, dd), 8.28 (1H, dd), 7.11 (4H, m), 6.95 (1H, d), 4.37 (2H, q), 1.38 (3H, t). MS (ES): MH+ 262.2.

Provenance & Evidence