Acetonitrile → Methyl 4-acetamido-3-chloro-6-(2,5-difluoro-4-(trimethylsilyl)phenyl)picolinate

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In a microwave vessel, a suspension of (2,5-difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)trimethylsilane (see, e.g., WO 2013003740 A1) (1 g, 2.56 mmol), methyl 4-acetamido-3,6-dichloropicolinate (Head L) (0.562 g, 2.135 mmol), bis(triphenyl phosphine)palladium(II) chloride (0.150 g, 0.214 mmol) and sodium carbonate (0.272 g, 2.56 mmol) in a 3:1 mixture of acetonitrile (5.34 mL) and water (1.779 mL) was stirred under microwave irradiation (120° C., 20 min). The reaction mixture was poured into an half saturated brine solution and was extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by preparative reverse phase HPLC (water/acetonitrile gradient) to afford the title compound as a white solid (0.481 g, 1.165 mmol, 54.6%): mp 135-137° C.; 1H NMR (400 MHz, CDCl3) δ 9.07 (d, J=0.8 Hz, 1H), 7.96 (s, 1H), 7.62 (dd, J=8.5, 5.7 Hz, 1H), 7.13 (dd, J=10.5, 4.1 Hz, 1H), 4.02 (s, 3H), 2.33 (s, 3H), 0.33 (d, J=0.8 Hz, 9H); 19F NMR (376 MHz, CDCl3) δ −106.66, −106.72, −123.42, −123.48; ESIMS m/z 411 ([M−H]−).

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