公开(公告)号：US06670477B2

公开(公告)日：2003-12-30

申请号：US10090087

申请日：2002-03-04

申请人： Wen-Chung Shieh ,  Song Xue ,  Noela Marjory Reel ,  John Joseph Fitt

发明人： Wen-Chung Shieh ,  Song Xue ,  Noela Marjory Reel ,  John Joseph Fitt

IPC分类号： C07D21122

CPC分类号： C07D211/34 ,  Y02P20/55

摘要： A process for making enantiomerically enriched 4-piperidinylglycine having the formula (I), said process comprising (a) combining N-protected glycine ester with 4-piperidone to form didehydroamino acid ester; (b) reducing the didehydroamino acid ester with hydrogen gas in the presence of a rhodium catalyst selected from the group consisting of (R,R)-BPE-Rh; (S,S)-BPE-Rh; (R,R)-DuPHOS-Rh; (S,S)-DuPHOS-Rh; and combinations thereof; whereby a protected compound is formed; and (c) removing the protecting groups from the protected compound, whereby the 4-piperidinylglyeine having the formula (I) is formed, wherein X− is an anion wherein X is independently a halogen; and “*” designates an asymmetric carbon having (R)- or (S)-configuration. The process of the invention yields an enantiomerically enriched (R)-4-piperidineglycine or (S)-4-piperidineglycine.

摘要翻译： 制备具有式（I）的对映体富集的4-哌啶基甘氨酸的方法，所述方法包括（a）将N-保护的甘氨酸酯与4-哌啶酮组合以形成二氢氨基酸酯; （b）在选自（R，R）-BPE-Rh的铑催化剂存在下，用氢气还原二氢氨基酸酯; （S，S）-BPE-Rh; （R，R）-DuPHOS-Rh; （S，S）-DuPHOS-Rh; 及其组合; 从而形成受保护的化合物; 和（c）从保护的化合物中除去保护基，由此形成具有式（I）的4-哌啶基甘氨酸，其中X 1是阴离子，其中X独立地是卤素; 和“*”表示具有（R） - 或（S） - 构型的不对称碳。 本发明的方法产生对映异构体富集的（R）-4-哌啶甘氨酸或（S）-4-哌啶甘氨酸。