Purification of Difluoromethylornithine by Global Process Optimization: Coupling of Chemistry and Chromatography with Enantioselective Crystallization

Autor:	Elias Ndzie, Wilhelm Hauck, Olivier Ludemann-Hombouger, William H. Pirkle, Jean Blehaut, Scott R. Perrin, Roger-Marc Nicoud
Rok vydání:	2007
Předmět:	Chromatography Chemistry Organic Chemistry Enantioselective synthesis Chemical modification Chiral resolution law.invention chemistry.chemical_compound law Lactam Organic chemistry Process optimization Physical and Theoretical Chemistry Crystallization Enantiomer Enantiomeric excess
Zdroj:	Organic Process Research & Development. 11:817-824
ISSN:	1520-586X 1083-6160
DOI:	10.1021/op700118m
Popis:	An industrial process for the purification of metric tons of enantiomerically pure difluoromethylornithine (DFMO HCl) is described. The amino acid DFMO HCl is cyclized to form the lactam, which is acylated with pivaloyl chloride to form rac-N-pivaloyl-DFMO lactam (4). The lactam 4 provides enhanced separation compared to a direct resolution of racemic DFMO HCl (1). A hybrid chiral resolution process is proposed to separate the enantiomers of 4. This process involves a multicolumn continuous enantioselective chromatographic process (VariCol) coupled with enantioselective crystallization of (d)-N-pivaloyl-DFMO lactam 5. The interest of this hybrid process is based on a favorable eutectic point providing a higher productivity of the VariCol process and lower purification costs than the chromatographic process alone. A final chemical modification (hydrolysis) is used to form the single enantiomers of both (d)-DFMO (6) and (l)-DFMO in high chemical purity and enantiomeric excess. A global optimization approach...
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::6949896cf55cd29041a1ce78a93c39a0 https://doi.org/10.1021/op700118m Zobrazit plný text záznamu