盐酸左布诺洛尔的合成工艺改进

Improved synthesis of levobunolol hydrochloride

以 5 羟基 α 萘满酮与R 环氧氯丙烷反应 ,生成中间产物 5 (2 ,3 环氧丙氧基 ) α 萘满酮 ,不经分离 ,直接加入叔丁基胺反应得游离碱 ,盐酸成盐后得到了盐酸左布诺洛尔。该工艺路线可简化反应 ,使产率达到 6 0 % ,光学纯度大于 90 %。

S -5-(2,3-epoxypropoxy)-3,4-dihydro-1( 2H )-naphthalenone(2) was got by the reaction of 5-hydroxy-3,4-dihydro-1( 2H )-naphthalenone with R -(-)-epichlorhydrin.The intermediate can be used directly to react with tertbutylamine to give( S )-(-)-5-[3-(tertbutylamino)-2-hydroxypropoxy]-3,4-dihydro-1( 2H )-naphthalenone without separating 2 from the system.At the same time a higher overall yield(60%)was got than that in the previous report with a high optical purity above 90%.