1,2-Dichloroethane → 2-Amino-5-fluoro-N-methoxy-N-methylbenzamide

Participants

Reaction Steps

To a 0° C. mixture of N,N-diisopropylethylamine (13.47 mL, 77 mmol) and N,O-dimethylhydroxylamine hydrochloride (7.55 g, 77 mmol) in CHCl3 (117 mL) was added 2-amino-5-fluorobenzoic acid (10.00 g, 64.5 mmol) followed by EDC (12.36 g, 64.5 mmol). The reaction was stirred from 0° C. to rt. After 22 h, the mixture was diluted with DCM (100 mL) and washed with aq satd NaHCO3 (1×100 mL), brine (1×100 mL), and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as a brown syrup. The crude material was purified by silica gel column chromatography eluting with a gradient of 0% to 100% EtOAc in hexane, to provide 2-amino-5-fluoro-N-methoxy-N-methylbenzamide as a yellow oil: 1H NMR (400 MHz, DMSO-d6) δ ppm 6.97-7.04 (2H, m), 6.72 (1H, dd, J=9.4, 4.9 Hz), 5.22 (2H, s), 3.54 (3H, s), 3.22 (3H, s); LC-MS (ESI) m/z 199.0 [M+H]+.

Provenance & Evidence