Acetonitrile → Methyl 4-amino-6-(4-aminophenyl)-5-fluoro-3-vinylpicolinate

Participants

Reaction Conditions

Reaction Steps

In a microwave vessel, a suspension of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (commercially available) (0.617 g, 2.82 mmol), methyl 4-amino-6-chloro-5-fluoro-3-vinylpicolinate (Head G) (0.5 g, 2.168 mmol), bis(triphenyl phosphine)palladium(II) chloride (0.152 g, 0.217 mmol) and potassium fluoride (0.327 g, 5.64 mmol) in a 1:1 mixture of acetonitrile (3.61 mL) and water (3.61 mL) was stirred under microwave irradiation (120° C., 20 min). The reaction mixture was poured into a 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 flash column chromatography (SiO2 24 g, hexanes/EtOAc gradient) to afford the title compound as a yellow solid (0.552 g, 89%) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ 7.60-7.58 (m, 2H), 6.72 (dd, J=17.7, 11.5 Hz, 1H), 6.65-6.58 (m, 2H), 6.24 (s, 2H), 5.47 (s, 2H), 5.45 (dd, J=11.5, 1.2 Hz, 1H), 5.38 (dd, J=17.7, 1.2 Hz, 1H), 3.77 (s, 3H); 19F NMR (376 MHz, DMSO-d6) δ −146.62; ESIMS m/z 286 ([M−H]−).

Provenance & Evidence