An improved synthesis of enantiomerically pure RWJ 69442, a development candidate for the treatment of benign prostatic hyperplasia

Abstract This report describes an improved synthesis of enantiomerically pure ( S )‐2‐[4‐(Dimethylamino)phenyl]‐2,3‐dihydro‐ N ‐[2‐hydroxy‐3‐[4‐[2‐(1‐methylethoxy)‐phenyl]‐1‐piperazinyl]propyl]‐1,3‐dioxo‐1 H ‐isoindole‐5‐carboxamide (RWJ 69442), a potent and selective α la ‐adrenergic receptor antagonist for the treatment of benign prostatic hyperplasia. The synthesis highlights less hazardous reagents, easier purification and higher enantiomeric purity. The N ‐benzyl‐ N—t ‐butoxycarbonyl amine 6 could serve as an enantiomerically pure chiral building block for asymmetric synthesis.