Hydrochloric Acid → 4-Amino-3-chloro-6-(4-chloro-3-ethoxy-2-fluorophenyl)-5-fluoropicolinic acid

Participants

Reaction Conditions

Reaction Steps

4-Amino-3-chloro-6-(4-chloro-3-ethoxy-2-fluorophenyl)-5-fluoropicolinic acid. A 2 M solution of aqueous NaOH (900 μL, 1.8 mmol, 4.0 equiv) was added to a stirred suspension of methyl 4-amino-3-chloro-6-(4-chloro-3-ethoxy-2-fluorophenyl)-5-fluoropicolinate (170 mg, 0.45 mmol, 1.0 equiv) in methyl alcohol (3.0 mL) at 23° C. The resulting heterogeneous white mixture was stirred at 23° C. for 4 h. The reaction mixture was adjusted to approximately pH=4 via dropwise addition of concentrated HCl and then concentrated via rotary evaporation. The residue was slurried in water and vacuum filtered to afford the desired product, 4-amino-3-chloro-6-(4-chloro-3-ethoxy-2-fluorophenyl)-5-fluoropicolinic acid as a white powder (140 mg, 88%): mp 163-165° C.; IR (thin film) 3486 (m), 3377 (s), 3155 (w), 2981 (w), 2935 (w), 1718 (s), 1614 (s) cm−1; 1H NMR (300 MHz, DMSO-d6) δ 7.45 (dd, J=9, 2 Hz, 1H), 7.28 (dd, J=9, 7 Hz, 1H), 7.01 (br s, 2H), 4.15 (q, J=7 Hz, 2H), 1.33 (t, J=7 Hz, 3H); ESIMS m/z 363 ([M+H]+).

Provenance & Evidence