(R)-1-(4-苄氧基-3-硝基苯基)-2-溴乙醇制备工艺的改进

New Preparation Process for (R)-1-(4-Benzyloxy-3-nitrophenyl)-2-Bromoethanol

以4-苄氧基-3-硝基-α-溴代苯乙酮为原料,在聚苯乙烯磺酰胺化固载的(R)-二苯基脯氨醇形成的唑硼烷催化下,经NaBH4/Me3SiCl不对称还原制得了(R,R)-福莫特罗的关键中间体(R)-1-(4-苄氧基-3-硝基苯基)-2-溴乙醇,收率95%,ee值95.4%。手性氨基醇可以方便的分离和回收利用,降低了生产成本。用NaBH4/Me3SiCl为还原剂代替BH3,降低了毒性,提高了安全性。

（R）-1-（4-Benzyloxy-3-nitrophenyl）-2-bromoethanol, a key intermediate for the preparation of （R, R）-formoterol, was prepared from 4-benzyloxy-3-nitrophenyl-α-bromoacetophenone using BH3 complex with polymer-bonded （R）-diphenylpyrrolidinemethanol as the catalyst and NaBH4/Me3 SiC1 as reduetant via an enantioseleetive reduction. The yield and ee value for the reaction are 95% and 95.4% respectively. The resulted ehiral compounds can be easily separated and recycled, which reduce the production cost. Using NaBH4/Me3SiCl as the reduetant could minimize the toxicity of the reaction and help to improve the safety issue.