Abstract: （S, R, R, R）-nebivolol is a novel and effective β<SUB<1</SUB<-adrenergic antagonist with antihypertensive activity. The oxidation/Wittig olefination "one-pot" and the Sharpless asymmetric epoxidation/cyclization "one-pot" are adopted in this route of synthesis. 1-6-fluoro-（2S）-3,4-dihydro-2H-2-chromenyl-（1R）-1,2-ethanediol and 1-6-fluoro-（2R）-3,4-dihydro-2H-2-chromenyl-（1S）-1,2-ethanediol, the two key intermediates of nebivolol, are obtained in eight steps by the asymmetric synthesis route. The synthesis protocol is convenient and each step has a high yield, thus the overall yield can reach 19%.