Potassium Carbonate → Methyl 2-(2-fluoro-4-(trifluoromethoxy)phenyl)isonicotinate

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Reaction Conditions

Reaction Steps

Methyl 2-chloroisonicotinate (3 g, 17.48 mmol), 2-(2-fluoro-4-(trifluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (5.37 g, 17.55 mmol), potassium carbonate (1.812 g, 13.11 mmol) and PdCl2 (dppf) (0.380 g, 0.52 mmol) were mixed in methanol (30 mL) in two separate 20 mL microwave vials. The vials were capped and heated at 100° C. for 10 min in a single node microwave reactor. Water and DCM were added and the phases were separated. The aqueous phase was extracted with DCM and the combined organic layers were filtered through a phase separator and evaporated to yield a dark-brown solid. The residue was purified by automated flash chromatography on a Biotage® KP-SIL 340 g column. A gradient from 8:1 to 3:1 of EtOAc in heptane over 10 CV was used as mobile phase. Methyl 2-(2-fluoro-4-(trifluoromethoxy)phenyl)isonicotinate (4.48 g, 81%) was yielded as a colorless solid. 1H NMR (600 MHz, cdcl3) δ 3.96 (s, 3H), 7.07 (d, 1H), 7.14 (d, 1H), 7.79-7.84 (m, 1H), 8.03-8.09 (m, 1H), 8.31 (s, 1H), 8.82-8.88 (m, 1H). MS m/z 316 (M+H)+

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