3-Fluorophenol → HCID 69418367, compound

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)+.

1. temperatureThe resulting mixture was heated
2. temperatureat reflux temperature for 16 h
3. customwith azeotroping
4. additionThe mixture was poured into water (50 mL)
5. extractionthe aqueous mixture was extracted with ethyl acetate (100 mL)
6. washThe organic extracts were washed with water (50 mL) and brine (50 mL)
7. dry with materialdried (sodium sulfate)
8. concentrationconcentrated under reduced pressure

ORD record

ord-805aa70323dc474fae9d5df015bb7fff

Source dataset

uspto-grants-2007_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07238714B2