Chin. J. Org. Chem. ›› 2009, Vol. 29 ›› Issue (08): 1254-1258. Previous Articles     Next Articles

Original Articles

(R)-(+)-5-甲基-5-{4-[2-(2-(5-氯吲唑基))乙氧基]苄基}-2,4-噁唑烷二酮的合成及其绝对构型的确定

李雅潇a; 马慧勇a ; 林紫云a; 王经斌a; 杨世颖a ;
张艳红b ; 吕 扬a ; 黄海洪*,a
  

  1. (a中国医学科学院中国协和医科大学药物研究所 北京 100050)
    (b国家新药开发工程技术研究中心 北京 102600)
  • 收稿日期:2009-03-17 修回日期:2009-04-27 发布日期:2009-08-30
  • 通讯作者: 黄海洪

Synthesis and Determination of Absolute Configuration of (R)-(+)-5-{4-[2-(5-Chloroindazol-2-yl)ethoxy]benzyl}- 5-methyl-2,4-oxazolidinedione

Li, Yaxiaoa; Ma, Huiyonga ; Lin, Ziyuna ; Wang, Jingbina; Yang, Shiyinga;
Zhang, Yanhongb ; Lü, Yanga; Huang, Haihong*,a
  

  1. (a Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050) (b National Engineering Research Center for the Development of New Drugs, Beijing 102600)
  • Received:2009-03-17 Revised:2009-04-27 Published:2009-08-30
  • Contact: Huang, Haihong

The chiral α-hydroxyester 4 was obtained by acid catalyzed esterification of the corresponding α-hydroxylacid that was resolved by (S)-(-)-1-phenylethylamine. After cyclization and deprotection, the key intermediate (R)-(+)-5-methyl-5-(4-hydroxybenzyl)-2,4-oxazolidinedione (6) was obtained. The novel title compound 9 was obtained by the condensation of 6 with methanesulfonate 8. The structure of 9 was confirmed by 1H NMR and HRMS techniques, and its absolute configuration was derived from the X-ray diffraction of R enantiomer of 3.

Key words: chemical resolution, single-crystal X-ray diffraction, absolute configuration, 2,4-oxazolidinedione