Methyl 2-amino-5-bromobenzoate → Methyl 2-amino-5-cyanobenzoate

Participants

Reaction Conditions

Reaction Steps

Copper(I) cyanide (available from Alfa Aesar; 10.71 g, 0.12 mol) was added to a stirred solution of methyl 2-amino-5-bromobenzoate (available from Aldrich Chemical Company, Inc.; 25.0 g, 0.11 mol) in N-methyl-2-pyrrolidone (50 mL) and the mixture was stirred at 180° C. for 4 h. The reaction mixture was cooled to room temperature, diluted with aqueous ethylenediamine (water:ethylenediamine=1:1; 250 mL), and filtered through pad of Celite. The filtrate was extracted with EtOAc (3×100 mL), and the combined organic layers were washed with water (100 mL) and brine (100 mL), dried over sodium sulfate, filtered, evaporated under reduced pressure, and purified by silica gel chromatography (100-200 mesh), using 5-10% ethyl acetate/hexanes as eluent, to give 2-amino-5-cyanobenzoic acid methyl ester (14.0 g, 73%) as a yellow powder. 1H NMR (400 MHz, DMSO-d6) δ 8.05 (d, J=1.9 Hz, 1H), 7.57 (dd, J=1.9, 8.8 Hz, 1H), 7.44 (br s, 2H), 6.88 (d, J=8.8 Hz, 1H), 3.81 (s, 3H).

Provenance & Evidence