Ethanol → Ethyl 4-amino-6-(4-chloro-2-fluoro-3-methoxyphenyl)-3-(difluoromethoxy)picolinate

Participants

Reaction Conditions

Reaction Steps

2-Chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)-3-(difluoromethoxy)pyridin-4-amine (0.2 g, 0.566 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) ((C17H14P)2Fe·PdCl2; 0.041 g, 0.057 mmol), and triethylamine (Et3N, 0.158 mL, 1.133 mmol) were combined in EtOH (5 mL) in a 45 mL bomb reactor. The bomb reactor was pressurized to 400 pounds per square inch (psi) with carbon monoxide (CO) and the reaction was heated at 105° C. for 40 h. The reaction mixture was then filtered through a small plug of silica gel utilizing EtOAc as the eluent. The filtrate was concentrated, and the product was purified by column chromatography (SiO2, hexane/EtOAc gradient) to yield the title compound as a white solid (79 mg, 35.7%): 1H NMR (300 MHz, CDCl3) δ 7.66 (dd, J=8.6, 7.7 Hz, 1H), 7.28-7.24 (m, 1H), 7.22 (d, J=1.7 Hz, 1H), 6.72 (t, J=75.1 Hz, 1H), 4.73 (s, 2H), 4.46 (q, J=7.1 Hz, 2H), 3.97 (d, J=0.8 Hz, 3H), 1.42 (t, J=7.2 Hz, 3H); ESIMS m/z 391 ([M+H]+), 389 ([M−H]−); 19F NMR (376 MHz, CDCl3) δ −79.74, −132.19.

Provenance & Evidence