Potassium Carbonate → Methyl 5-chloro-2-(3-fluorophenyl)nicotinate

Participants

Reaction Conditions

Reaction Steps

A solution of methyl 2,5-dichloronicotinate (27.0 g, 131 mmol), (3-fluorophenyl)boronic acid (20.2 g, 144 mmol), and potassium carbonate (39.5 g, 286 mmol) in water (190 mL) and 1,4-dioxane (578 mL) was degassed with nitrogen (10 min). The reaction mixture was treated with bis(triphenylphosphine)palladium(II) chloride (5.2 g, 7.4 mmol), degassed with nitrogen (10 min), and heated at 80° C. for 18 hours. The reaction was complete, allowed to cool to room temperature and partitioned between ethyl acetate and water. The combined organic layer was washed with water, brine, dried over magnesium sulfate, filtered, and concentrated to give the crude residue product as a dark oil. The product was purified on silica gel eluting with hexane:ethyl acetate gradient to give methyl 5-chloro-2-(3-fluorophenyl)nicotinate (27.5 g, 79%) as a white solid. LCMS calculated for C13H10ClFNO2(M+H)+: m/z=266.0. found: 265.9.

Provenance & Evidence