Hydrochloric Acid → 5-Bromo-3-[(2,2-difluoroethyl)amino]thiophene-2-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 5-bromo-3-[(2,2-difluoroethyl)amino]thiophene-2-carboxylate (285 mg, 0.95 mmol) in MeOH (3.0 mL) was added a solution of sodium hydroxide (114 mg, 2.85 mmol) in water (1.5 mL). After stirring at 60° C. for 4 h, 6 M aqueous HCl (0.3 mL) was added to the mixture to adjust the pH to 10. After removal of the solvent at reduced pressure, the residue was diluted with DMF (5 mL). Then, triethylamine (2.6 mL, 19 mmol) and ammonium chloride (1.02 g, 19 mmol) were added. After stirring at room temperature for 5 min, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.09 g, 5.70 mmol) and 1-hydroxybenzotriazole (0.77 g, 5.70 mmol) were added to the mixture and the stirring was continued for 17 h. Then, water and EtOAc were added to quench the reaction. The organic materials were extracted with EtOAc. The combined extracts were washed with water and brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, hexane to 70:30 hexane/EtOAc) to give the title compound (130 mg, 48%) as a yellow solid:

Provenance & Evidence