851029-10-2Relevant academic research and scientific papers
Development of a kilogram-scale synthesis of cis-LC15-0133 tartrate, a potent dipeptidyl peptidase IV inhibitor
Kim, Bong Chan,Kim, Kyu-Young,Lee, Hee Bong,Shin, Hyunik
, p. 626 - 631 (2008)
(45)-N-Boc-4-fluoro-L-proline methyl ester (4) was prepared from the following sequence of reactions: esterification of trans-4-hydroxy-L-proline (2), Boc protection, and fluorination by DAST. Reaction of 4 with lithiated oxadiazole provided oxadiazolyl ketone 7. Deprotection of the Boc group of 7 and subsequent coupling with bromoacetyl bromide gave bromide 9. Coupling reaction of 9 with excess oxazolidine 16 provided coupled product 17. Unexpectedly, the stereogenic center of 17 was completely epimerized to a virtually 1:1 mixture of cis- and trans-17 at this stage. After the deprotection of the N,O-methylene acetal group of 17 using aqueous ammonium chloride, crystallization induced dynamic resolution (CIDR) of cis- and Awns-mixture of LC15-0133 (1) in the course of tartrate salt formation provided cis-LC15-0133 (1a) tartrate salt in 83% yield (>98% de).
