Practical Synthesis of Elacestrant, an FDA‐Approved Selective Estrogen Receptor Degrader

Herein, we report an efficient and scalable synthesis of the core skeleton of elacestrant, a selective estrogen receptor degrader used in breast cancer treatment. The present synthesis features simple synthetic transformations, involving one‐pot conversion of 6‐hydroxy‐1‐tetralone into a cyclic olefin followed by copper‐catalyzed arylation of the cyclic olefin (iodometathesis) with a diaryliodonium salt as a key strategy to achieve the core skeleton on a gram scale. This procedure was extended to the total synthesis of (±)‐elacestrant by employing two different coupling strategies: reductive amination of an aldehyde and nucleophilic substitution of a bromo compound with the core skeleton.