乙胺丁醇的合成

对手性抗结核药物盐酸乙胺丁醇的关键中间体———乙胺丁醇的合成进行了系统研究。以1 丁烯、氯气和乙腈为原料,合成了(R,S) 2 氨基丁醇,收率50 7%;选用L (+) 酒石酸拆分(R,S) 2 氨基丁醇,得到酸式(S) 2 氨基丁醇的L (+) 酒石酸盐,收率94 3%;滤液经处理后,得到酸式(R) 2 氨基丁醇的L (+) 酒石酸盐,收率99 0%;将两种酸式2 氨基丁醇的L (+) 酒石酸盐分别进行水解,得到(S) 2 氨基丁醇和(R) 2 氨基丁醇,收率均达85 0%以上;最后,以(S) 2 氨基丁醇和1,2 二氯乙烷为原料,合成了乙胺丁醇,收率81 3%。此外,选用骨架镍催化剂,对(R) 2 氨基丁醇进行了消旋化反应,收率72 7%;将水解得到的酒石酸钠晶体用于L (+) 酒石酸的回收,收率82 5%。

Synthesis of Ethambutol

Ethambutol is the key intermediate of ethambutol hydrochloride which is used as a chiral antituberculosis agent.(R,S)-2-Aminobutanol was synthesized from 1-butene,chlorine and acetonitrile in a yield of 50.7%.Resolution of (R,S)-2-aminobutanol with L-(+)-tartaric acid gave(S)-2-aminobutanol L-(+)-tartrate in 94.3% yield,and (R)-2-aminobutanol L-(+)-tartrate was produced in 99.0% yield after the treatment of the filtrate.The optically pure (S)-2-aminobutanol and (R)-2-aminobutanol were both obtained in over 85.0% yield after the hydrolysis of (S)- and (R)-2-aminobutanol L-(+)-tartrate separately.Finally,ethambutol was obtained in 81.3% yield from (S)-2-aminobutanol and 1,2-dichloroethane.Furthermore,racemization of (R)-2-aminobutanol using Raney Ni as catalyst afforded (R,S)-2-aminobutanol in a yield of 72.7%.L-(+)-Tartaric acid was recovered in a yield of 82.5% from sodium tartrate which was obtained through the hydrolysis of 2-aminobutanol L-(+)-tartrate.