Ethyl bromodifluoroacetate → (4-Amino-3-methyl-5-nitro-phenyl)-difluoro-acetic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-iodo-2-methyl-6-nitroaniline (2.78 g, 10 mmol) and 2-bromo-2,2-difluoroacetic acid ethyl ester (2.03 g, 10 mmol) in anhydrous DMSO (20 mL) was added copper powder (1.28 g, 20 mmol). The mixture was purged with N2 and heated at 60° C. in a sealed vial for 14 h. After being cooled to the room temperature, the reaction mixture was poured into 20% aqueous NH4Cl solution (300 mL). The resulting mixture was basified to pH=8.5 with saturated aqueous Na2CO3 solution and was extracted with EtOAc (3×100 mL). The organic extract was washed with brine (2×30 mL), dried over Na2SO4 and concentrated. The residue was purified by chromatography (40:1 hexanes/EtOAc) to afford the title compound (1.79 g, 65%). 1H NMR (CDCl3) δ 1.36 (t, 3H), 2.30 (s, 3H), 4.36 (q, 2H), 6.41 (br s, 2H NH), 7.51 (s, 1H), 8.33 (s, 1H). ESI-MS m/z 275 (MH+), 255 (M-F)+, 297 (M+Na)+, 549 (2M+1)+ and 571 (2M+Na)+.

Provenance & Evidence