Synthesis
General procedure for the synthesis of 2-acetamido-5-bromothiophene from the compound (CAS: 98453-21-5): to a solution of ketoxime (0.01 mol) in tetrahydrofuran (THF, 10 mL) was added tripropylphosphinic anhydride (T3P, 15 mol%, 50% dissolved in ethyl acetate (EtOAc)), and the reaction mixture was heated under nitrogen protection at refluxed and stirred for 1-4 hours. The progress of the reaction was monitored by thin layer chromatography (TLC) and after confirming the completion of the reaction, the solvent was evaporated under reduced pressure. The residue was diluted with distilled water (20 mL) and subsequently extracted with ethyl acetate (2 x 20 mL). The organic phases were combined and washed sequentially with saturated sodium bicarbonate (NaHCO3) solution (10 mL) and saturated sodium chloride (brine) solution. The organic phase was dried over anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure to afford the target product 2-acetamido-5-bromothiophene with high purity.
References
[1] Journal of Heterocyclic Chemistry, 1985, vol. 22, p. 301 - 304
[2] Tetrahedron Letters, 2011, vol. 52, # 10, p. 1074 - 1077
[3] Journal of Medicinal Chemistry, 2016, vol. 59, # 19, p. 8830 - 8847
[4] Synthesis, 2006, # 8, p. 1295 - 1300
