Sodium Hydroxide → HCID 69417684, compound

Participants

Reaction Steps

To a stirred solution of methyl 2,5-dichloronicotinate (J. Med. Chem. 1993, 36, 2676, 353 mg, 1.71 mmol) and 3-fluorophenol (291 mg, 2.6 mmol) in toluene (5 mL) was added potassium carbonate (360 mg, 2.6 mmol) in one portion. The resulting mixture was heated at reflux temperature for 16 h with azeotroping using a Dean Stark apparatus. The mixture was poured into water (50 mL) and the aqueous mixture was extracted with ethyl acetate (100 mL). The organic extracts were washed with water (50 mL) and brine (50 mL), dried (sodium sulfate), and concentrated under reduced pressure to give crude methyl 5-chloro-2-(3-fluorophenoxy)nicotinate. To a stirred solution of the crude ester in methanol (10 mL) was added 2 N sodium hydroxide aqueous solution (2 mL). The reaction mixture was stirred at room temperature for 3 h. The reaction mixture was partitioned between ether (30 mL) and water (30 mL). The organic phase was separated and the aqueous phase was acidified with 2 N hydrochloric acid (10 mL). The acidic mixture was extracted with dichloromethane (50 mL×3). The combined organic layer was washed with brine (100 mL), dried (sodium sulfate), and concentrated to afford 448 mg (93%) of the title compound as off white solids: 1H-NMR (CDCl3) δ 8.44 (1H, d, J=2.6 Hz), 8.26 (1H, d, J=2.6 Hz), 7.46–7.36 (1H, m), 7.07–6.89 (3H, m); MS (ESI) m/z 268 (M+H)+.

Provenance & Evidence