1,2-Dimethoxyethane → Methyl 4-acetamido-3-(benzyloxy)-6-(4-chloro-2-fluoro-3-methoxyphenyl)picolinate

関与物質

反応条件

反応手順

Methyl 4-acetamido-3-(benzyloxy)-6-bromopicolinate (prepared as in Kong, L. C. C. et al. U.S. Patent Application Publication 2005/0176767; 1.5 g, 4.0 mmol), (4-chloro-2-fluoro-3-methoxyphenyl)boronic acid (1.2 g, 5.9 mmol), bis(triphenylphosphine)-palladium(II) dichloride (PdCl2(PPh3)2; 278 mg, 0.4 mmol), cesium fluoride (CsF; 1.2 g, 7.9 mmol), 1,2-dimethoxyethane (DME; 7 mL), and H2O (7 mL) were combined and heated in a Biotage microwave at 100° C. for 15 min. H2O was added to the reaction mixture, and the product was extracted with EtOAc. The combined organic extracts were washed with satd aq NaCl, dried with sodium sulfate (Na2SO4), filtered and concentrated. Flash chromatography (SiO2; 0-45% EtOAc/cyclohexane gradient) afforded methyl 4-acetamido-3-(benzyloxy)-6-(4-chloro-2-fluoro-3-methoxyphenyl)picolinate as a yellow solid: mp 115-120° C.; 1H NMR (400 MHz, CDCl3) δ 8.87 (d, J=1.6 Hz, 1H), 7.66 (s, 1H), 7.59 (dd, J=8.5, 7.7 Hz, 1H), 7.45 (s, 5H), 7.24 (dd, J=8.6, 1.7 Hz, 1H), 5.13 (s, 2H), 4.03 (s, 3H), 3.99 (d, J=1.0 Hz, 3H), 1.88 (s, 3H); ESIMS m/z 459 ([M+H]+).

情報源と証拠