Potassium Fluoride → Methyl 4-acetamido-6-(4-amino-2,3,6-trifluorophenyl)-3-chloropicolinate

Participants

Reaction Conditions

Reaction Steps

A suspension of methyl 4-acetamido-3-chloro-6-(trimethylstannyl)picolinate (Head K) (0.502 g, 1.409 mmol, 1.0 eq), 2,3,5-trifluoro-4-iodoaniline (0.5 g, 1.831 mmol, 1.3 eq), bis(triphenylphosphine)palladium(II) chloride (0.098 g, 0.1401 mmol, 0.1 eq) and CuI (26 mg, 0.1401 mmol, 0.1 eq) in dry DMF (3 mL) was irradiated with microwave at 120° C. for 1 h. Reaction mixture was cooled to 20° C. and stirred with aqueous KF solution (20 mL) for 15 m and extracted with ethyl acetate (3×100 mL). The combined organic layers were dried over anh. Na2SO4, filtered and evaporated to dryness under reduced pressure. The crude product was purified on silica gel (60-120) using a gradient from 0-30% EtOAc in hexanes yielded the title compound as a brown solid (280 mg, 44.8%): 1H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 8.32 (s, 1H), 6.51-6.46 (m, 1H), 6.22 (brs, 2H), 3.92 (s, 3H), 2.23 (s, 3H); ESIMS m/z 376 ([M+3H]+).

Provenance & Evidence