Hydrochloric Acid → 2-(4-Bromo-2,5-dichloro-phenoxy)-nicotinic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-chloro-nicotinic acid (100 mg, 0.64 mmol, 1.0 equiv; [CAS RN 2942-59-8]) and 4-bromo-2,5-dichloro-phenol (184 mg, 0.76 mmol, 1.2 equiv; [CAS RN 1940-42-7]) in toluene (1 mL) was added caesium carbonate (517 mg, 1.59 mmol, 2.5 equiv; [CAS RN 534-17-8]) and tetrakis(acetonitrile)copper(I) hexafluorophosphate (47 mg, 0.13 mmol, 0.2 equiv; [CAS RN 64443-05-6]). The reaction mixture was heated by microwave irradiation to 140° C. for 1 h. The solvent was evaporated under reduced pressure and the crude reaction product taken up in water (100 mL) acidified to pH 1 by addition of a solution of 1 M HCl and extracted with ethyl acetate (3×100 mL). The combined organic phases were dried over MgSO4 and the product purified by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of dichloromethane/methanol affording 170 mg (73%) of the title compound as an off-white solid. 1H NMR (400 MHz, DMSO): δ7.21 (dd, J=−7.6 Hz, J=4.8 Hz, 1H), 7.42 (s, 1H), 7.76 (s, 1H), 8.29 (dd, J=4.8 Hz, J=1.9 Hz, 1H), 8.50 (dd, J=7.7 Hz, J=2.0 Hz, 1H). MS (ISN): 362.0 [M−H]−.

Provenance & Evidence