Hydrogen Bromide → Ethyl5-bromo-1,3,4-thiadiazole-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

A 500 mL (three neck) round-bottom flask with a stir bar, needle inlet, and a gas outlet to a trap containing a 10% solution of Na2S2O3 was charged with CuBr (1.24 g, 8.67 mmol, 0.1 equiv.) and HBr (48% aqueous solution, 108 mL). The purple solution was cooled to 3° C. (internal, ice bath), to which was added portion-wise a solid mixture of 5-amino-[1,3,4]thiadiazole-2-carboxylic acid ethyl ester (15.0 g, 86.6 mmol) and sodium nitrite (27.0 g, 391.3 mmol, 4.5 equiv.) over the course of 30 min. The reaction mixture was allowed to warm to room temperature for 2 h 15 min. The reaction mixture was diluted with CH2Cl2 and 10% aqueous Na2S2O3 and the layers were separated. The aqueous layer was extracted 3 times with CH2Cl2. The combined organic layers were washed with Brine, dried over MgSO4, and concentrated. The crude product was purified by column chromatography (ISCO XL, 330 g SiO2 column, 20-25% EtOAc/Hexanes) to provide an off-white solid that was triturated with 5% EtOAc/Hexanes. Filtration provided 5-bromo-[1,3,4]thiadiazole-2-carboxylic acid ethyl ester (14.5 g, 71%) as white needles. Concentration and trituration of the mother liquor provided an additional product (2.3 g, 11%).

Provenance & Evidence