A Scalable synthesis of L-leucine-N-carboxyanhydride

N.M.B. Smeets, P.L.J. Weide, van der, J. Meuldijk, J.A.J.M. Vekemans, L.A. Hulshof

Research output: Contribution to journalArticleAcademicpeer-review

29 Citations (Scopus)
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Abstract

Due to its relevance in the synthesis of well-defined oligopeptides, the l-leucine-N-carboxyanhydride (leucine-NCA) synthesis was selected for fine chemical scale-up with a scope on application on larger scales. The heterogeneous gas-solid-liquid nature of the leucine-NCA synthesis implied a mass transfer limited reaction rate towards phosgenation and was investigated on bench scale. Upon scale increase, the liquid-gas mass transport of HCl is drastically reduced, retarding the reaction and consequently rendering the process unsuitable for scale-up. Addition of an HCl scavenger such as (+)-limonene prevented side reactions thus allowing a cost reduction, a considerably faster reaction, and minimization of the amount of phosgene source used. The modified leucine-NCA synthesis has successfully been made scalable, maintaining high product purity on a 1.0 dm3 scale.
Original languageEnglish
Pages (from-to)757-763
JournalOrganic Process Research & Development
Volume9
Issue number6
DOIs
Publication statusPublished - 2005

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