左沙丁胺醇盐酸盐的制备及其S-对映体的外消旋化

 目的制备左沙丁胺醇盐酸盐,并对拆分后得到的S-沙丁胺醇进行外消旋化。方法光学拆分剂L-酪氨酸与外消旋沙丁胺醇形成非映异构体盐,利用两者在甲醇-乙酸乙酯(1∶2)溶剂体系中溶解度的差异,完成两者的分离。去除L-酪氨酸后,分别得到R-和S-沙丁胺醇。左沙丁胺醇经过酸化,得到左沙丁胺醇盐酸盐。同时,在1 mol·L^-1硫酸溶液,80～90℃条件下,S-沙丁胺醇被外消旋化。结果拆分法得到左沙丁胺醇盐酸盐光学纯度99.1%(ennatiomer excess,EE),总收率为38.7%。S-沙丁胺醇经过外消旋化反应由85.5%EE转变为10.2%EE,收率83.0%。结论通过消旋化作用,S-沙丁胺醇产物可以重新回收利用,能大幅度提高左沙丁胺醇的收率,降低成本,该方法具有广阔的工业化前景。

Study on Preparation of Levalbuterol Hydrochloride and Racemization of S-Enantiomer

OBJECTIVE To prepare levalbuterol hydrochloride and make S-salbuterol racemized after the resolution.METHODS The racemic salbuterol and optical resolving agent L-tyrosine were interacted to the formation of diastereomer salt.In the methanol-ethyl acetate(1∶2) solvent system,two diastereomer salts were separated by their solubility differences,and after the remove of L-tyrosine,R-and S-salbuterol were obtained respectively.After acidification,levalbuterol chloride was prepared.Meanwhile,S-salbuterol was racemized at 80～90 ℃ in 1 mol·L^-1 sulfuric acid solution.RESULTS Levalbuterol chloride was 99.1% EE.And the total yield was 38.7%.S-salbuterol changed from the 85.5% EE to 10.2% EE after racemic reaction and the yield was 83.0%.CONCLUSION By the racemization,S-salbuterol can be recycled substantially,increasing the yield of levalbuterol and lowering costs.This method has cheerful prospects for industrialization.