Formic Acid → 2,3-Dichloro-N-{2-[formyl(Hydroxy)amino]ethyl}benzamide

Participants

Reaction Conditions

Reaction Steps

A mixture of acetic anhydride (5 mL) and formic acid (2.5 mL) was allowed to stand at 55° C. for 2.5 h. After cooling to 0° C., the resulting mixed anhydride was added to a solution of 2,3-dichloro-N-(2-hydroxyamino-ethyl)-benzamide (10.5 g, 42 mmol) in pyridine (50 mL) at 0° C. under an argon atmosphere. The reaction mixture was stirred for 2 h and the pyridine was removed in vacuo. The residue was chased three times with water and three times with MeOH. The residue was partitioned between cold brine/1N HCl and dichloromethane/MeOH (9:1). The aqueous layer was extracted (10×100 mL) with dichloromethane/MeOH (9:1). The combined organic extracts were dried (Na2SO4) and were concentrated. Purification by preparative reverse-phase HPLC provided the title compound (1.8 g, 15%) as a white solid. 1H NMR* (400 MHz, CD3OD): δ 8.35 (s, 0.5H); 7.95 (s, 0.5H); 7.60 (m, 1H); 7.35 (m, 2H); 3.79 (m, 1H); 3.73 (m, 1H); 3.62 (m, 2H). * 1:1 mixture of rotamers. ESMS: M+H=277.

Provenance & Evidence