Combinatorial chemistry. Preparation of phenoxypropanolamines

An efficient solid-phase parallel synthesis of aryloxypropanolamines is described. Mitsunobu coupling was used to attach (R)-(+)- and (S)-(−)-glycidol to resin-bound phenols, then the epoxide ring was opened with amines. A 25-member array was synthesized on Wang resin with a sarcosine handle. The overall yield was about 70%. A ‘split and mix’ approach was used to prepare a 5800-member bead bound combinatorial library on Rink amide resin. Magic angle NMR was used to monitor the reaction progress on the resin. Analysis by LC–MS revealed that >70% of the beads examined contained an identifiable product that was >70% pure by HPLC.