Practical asymmetric synthesis of a selective endothelin A receptor (ETA) antagonist

[GRAPHICS] A practical, chromotography-free asymmetric synthesis was developed for the large scale preparation of an endothelin receptor antagonist 2. This synth esis includes a new efficient process for the preparation of 6-bromo-2,3-di hydrobenzofuran, a stereoselective conjugate addition of an aryllithium fol lowed by stereospecific addition of the Grignard reagent of the top aryl br omide, and an aminophosphate-mediated sterospecific intramolecular enolate alkylation, which led to the formation of the five-membered ring bearing th ree contiguous asymmetric centers.