1,2-Dibromoethane → Methyl 5-bromo-3-(2,2,2-trifluoroacetamido)thiophene-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a stirred mixture of N-(1-methylethyl)propan-2-amine (40.0 mL, 285 mmol) and THF (400 mL) at −78° C. was added slowly 1.6 M n-butyllithium in hexane (165 mL, 264 mmol). The mixture was allowed to 0° C. over 2 h. Then, the mixture was cooled to −78° C. again. Then, a solution of methyl 3-[(trifluoroacetyl)amino]thiophene-2-carboxylate (20.3 g, 80 mmol) in THF (80 mL) was added to the mixture slowly. After 1 h, 1,2-dibromoethane (41.2 mL, 476 mmol) was added at once. The stirring was continued at −78° C. for 1 h, and the dry ice-acetone bath was removed. After further stirring for 30 min, the mixture was poured into saturated aqueous NaHCO3 (1 L) and EtOAc (1 L). After shaking well, the organic layer was collected, washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure to give an orange oil. This residue was purified by column chromatography (Purif, silica gel, hexane to 90:10 hexane/EtOAc) to afford the title compound (10.4 g, 39%) as a beige solid:

Provenance & Evidence