Toluene → Methyl 5-cyclopropyl-6-(2,2,2-trifluoroethoxy)nicotinate

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In a 50 mL two-necked flask, methyl 5-bromo-6-(2,2,2-trifluoroethoxy)nicotinate (1 g, 3.18 mmol, Eq: 1.00, CAN 1211589-51-3) and cesium carbonate (3.11 g, 9.55 mmol, Eq: 3) were combined with toluene (25 ml) and water (2.8 ml) to give a colorless solution. The reaction mixture was 3× degassed and purged with argon, then palladium(II) acetate (14.3 mg, 63.7 μmol, Eq: 0.02), potassium cyclopropyltrifluoroborate (518 mg, 3.5 mmol, Eq: 1.1) and butyldi-1-adamantylphosphine (68.5 mg, 191 μmol, Eq: 0.06) were successively added and the reaction mixture was heated to 120° C. for 5 h when TLC indicated that the reaction was complete. The mixture was cooled to rt, poured into 50 ml H2O and extracted with AcOEt (2×50 ml). The organic layers were washed with H2O/NaCl sol, combined, dried over Na2SO4 and concentrated in vacuo. Purification by flash chromatography (silica gel, 70 g, 0% to 20% EtOAc in heptane) yielded eventually 836 mg of the title compound as light yellow semisolid; MS (EI) 276.0 (M+H)+.

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