Potassium Fluoride → Methyl 4-amino-6-(4-chlorophenyl)-5-fluoro-3-methoxypicolinate

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 4-amino-6-chloro-5-fluoro-3-methoxypicolinate (200 mg, 0.852 mmol) in CH3CN (1.246 mL) and H2O (1.246 mL) were added 2-(4-chlorophenyl)-1,3,2-dioxaborinane (251 mg, 1.279 mmol), KF (149 mg, 2.56 mmol), palladium(II) acetate (Pd(OAc)2; 19.14 mg, 0.085 mmol), and triphenylphosphine-3,3′,3″-trisulfonic acid trisodium salt (100 mg, 0.170 mmol). The reaction mixture was then heated in a bench top Biotage microwave at 150° C. for 5 min. The reaction mixture was diluted with CH2Cl2 and washed with H2O. The organic layer was separated, dried over MgSO4, filtered and concentrated. The crude residue was purified by normal phase chromatography (eluting with 10% EtOAc/40% CH2Cl2/50% hexanes) to afford the title compound as a tan solid (191 mg, 72.1%): mp 93-94° C.; 1H NMR (400 MHz, acetone-d6) δ 7.96 (dd, J=8.8, 1.4 Hz, 2H), 7.57-7.49 (m, 2H), 5.93 (s, 2H), 3.92 (s, 3H), 3.91 (s, 3H), ESIMS m/z 311 ([M+H]+), 309 ([M−H]−).

Provenance & Evidence