Green and Strategic Approach for Chiral Resolution by Diastereomeric Salt Formation: The Study of Racemic Ibuprofen

Hung Lin Lee, Ying Lun Hung, Ahmed Amin, Dhanang Edy Pratama, Tu Lee

研究成果: 雜誌貢獻期刊論文同行評審

5 引文 斯高帕斯(Scopus)

摘要

As diastereomeric salt formation is the most popular method for the industrial preparation of single enantiomers, this method is chosen to resolve enantiomers of ibuprofen (IBU) in the present study. This type of chiral resolution process involves three steps: formation of a diastereomeric salt pair of racemic ibuprofen (Rac-IBU) with a chiral resolving agent, (S)-(−)-α-methylbenzylamine (S-MBA) in the presence/absence of a nonchiral agent, potassium hydroxide (KOH), resolution by cooling crystallization in a common solvent, and recovery of the compound with one enriched enantiomer. The present study is to investigate each of the three steps individually toward the chiral resolution of S-IBU, including the effects of (1) equivalent ratio of Rac-IBU-to-S-MBA-to-KOH on diastereomeric excess (%de) and yield upon the formation of the diastereomeric salts, (2) solvent and (3) temperature range for cooling crystallization on %de and yield upon the resolution by cooling crystallization, (4) solvent-to-antisolvent ratio, (5) aging time, and (6) addition rate of antisolvent on enantiomeric excess (%ee) and yield upon the recovery of the S-enriched IBU. Each step is optimized, and the integrated chiral resolution process is scaled up to a 0.5 L scale. Furthermore, practical guidelines are suggested for the future development of chiral resolution processes by diastereomeric salt formation.

原文???core.languages.en_GB???
頁(從 - 到)1946-1957
頁數12
期刊Industrial and Engineering Chemistry Research
62
發行號4
DOIs
出版狀態已出版 - 1 2月 2023

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