4-Ethoxy-1,1,1-trifluoro-3-buten-2-one (ETFBO), a Versatile Precursor for Trifluoromethyl-Substituted Heteroarenes – a Short Synthesis of Celebrex® (Celecoxib)The work was funded by the Deutsche Forschungsgemeinschaft (Cluster of Excellence REBIRTH; ‘From Regenerative Biology to Reconstructive Therapy’ EXC 62).
Received: 14 July 2017
Accepted after revision: 17 July 2017
22 August 2017 (eFirst)
4-Ethoxy-1,1,1-trifluoro-3-buten-2-one (ETFBO) serves as a trifluoromethyl-containing building block for the preparation of trifluoromethyl-substituted thiophenes, furans, pyrrols, and piperazines. Key steps are an addition–elimination reaction to ETFBO followed by the thiazolium-catalyzed Stetter reaction. The scope of this chemistry was demonstrated in a new synthetic approach towards the COX-2 selective, nonsteroidal anti-inflammatory drug Celebrex® (celecoxib).