Hydrochloric Acid → 5-(4-Chloro-3-fluorophenyl)-6-(2,2,2-trifluoroethoxy)nicotinic acid

Participants

Reaction Steps

5-Bromo-6-(2,2,2-trifluoroethoxy)-3-pyridinecarboxylic acid (4.00 g, 13.3 mmol; CAN 1211586-75-2) was dissolved in toluene (90 mL) and DMF (2.0 mL) to give a colorless solution. Then B-(4-chloro-3-fluorophenyl)-boronic acid (2.56 g, 14.7 mmol; CAN 137504-86-0), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (544 mg, 667 μmol) and aqueous sodium carbonate solution (53.3 ml, 107 mmol, 2 M) were successively added under stirring in an argon atmosphere. The reaction mixture was stirred 2.5 h at 90° C. Subsequently the reaction mixture was cooled to ambient temperature, poured into ice-water (300 mL), acidified with 2 N HCl (120 mL) and extracted with isopropyl acetate (3×200 mL). The organic layers were combined, dried with Na2SO4 and concentrated in vacuo. The residue was digested with a mixture of n-heptane and isopropyl acetate (10 mL/2 mL) at ambient temperature, filtered off and washed with isopropyl acetate/n-heptane 1:5 (2×3 ml). The resulting brown solid was digested with dichloromethane (10 mL) at ambient temperature to give the title compound (2.57 g, 55%) after filtration and drying as off-white solid; MS (EI) 347.9 (M+H)+.

Provenance & Evidence