Hydrochloric Acid → 3-Amino-5-bromothiophene-2-carboxamide

Participants

Reaction Conditions

Reaction Steps

A mixture of methyl 3-amino-5-bromothiophene-2-carboxylate (5.67 g, 24.0 mmol) was mixed with sodium hydroxide (2.94 g, 73.6 mmol), MeOH (100 mL) and water (25 mL) was stirred at 70° C. overnight. After cooling to 0° C., 6 M HCl (8.17 mL, 49.0 mmol) was added. This mixture was concentrated under reduced pressure to give a yellow solid. Co-evaporation was carried out with toluene and the resulting solid was dried under reduced pressure well. This residue was mixed with ammonium chloride (26.3 g, 491 mmol), triethylamine (49.7 g, 491 mmol) and DMF (230 mL). After stirred at room temperature for 5 min, 1-hydroxybenzotriazole (19.9 g, 144 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (28.2 g, 147 mmol) were added. The stirring was continued for 2 days. The reaction mixture was poured into saturated aqueous NaHCO3 (700 mL) and extracted with EtOAc (700 mL), and the extract was washed with saturated aqueous NaHCO3, dried over MgSO4, filtered and concentrated under reduced pressure. The residual brown oil was purified by column chromatography (Purif, silica gel, hexane to EtOAc) to afford the title compound (4.05 g, 75%) as yellow solid:

Provenance & Evidence