In a 50 mL two-necked flask, 5-bromo-6-(cyclopropylmethoxy)nicotinic acid (1 g, 3.68 mmol, Eq: 1.00, CAN 912454-38-7) and cesium carbonate (3.59 g, 11.0 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 (16.5 mg, 73.5 μmol, Eq: 0.02), potassium cyclopropyltrifluoroborate (598 mg, 4.04 mmol, Eq: 1.1) and butyldi-1-adamantylphosphine (79.1 mg, 221 μmol, Eq: 0.06) were successively added. The evacuating-purging cycle was repeated after each addition. The reaction mixture was then heated to 120° C. for 4 h when TLC indicated the presence of some remaining starting material. The same amount of palladium acetate and phosphine ligand was once more added, and the reaction allowed proceeding over night at 120° C. The mixture was cooled to rt, poured into 20 mL 1N NaOH and extracted with CH2Cl2 (2×20 mL). The aqueous layer was acidified with 30 mL 2N HCl and extracted with AcOEt (2×50 ml). The organic layers were washed with H2O/NaCl solution, combined, dried over Na2SO4 and concentrated in vacuo. Crystallization from AcOEt/heptane finally yielded 609 mg of the title compound as off-white solid; MS (EI) 232.6 (M−H)−.
