Chemoenzymatic Preparation of 1‐Heteroarylethanamines of Low Solubility

Abstract Both enantiomers of biologically and pharmaceutically interesting benzofuran‐, benzothiophen‐, and phenylfuran‐based 1‐heteroarylethanamines were prepared at close to theoretical yields by using Candida antarctica lipase B (Novozym 435) catalyzed ( R )‐selective N ‐acylation with isopropyl...

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Bibliographic Details
Published in:European Journal of Organic Chemistry
Main Authors: Brem, Jürgen, Bencze, László‐Csaba, Liljeblad, Arto, Turcu, Mihaela C., Paizs, Csaba, Irimie, Florin‐Dan, Kanerva, Liisa T.
Format: Article in Journal/Newspaper
Language:English
Published: Wiley 2012
Subjects:
Antarc*
Antarctica
Online Access:http://dx.doi.org/10.1002/ejoc.201200330
https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fejoc.201200330
http://onlinelibrary.wiley.com/wol1/doi/10.1002/ejoc.201200330/fullpdf
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Summary:Abstract Both enantiomers of biologically and pharmaceutically interesting benzofuran‐, benzothiophen‐, and phenylfuran‐based 1‐heteroarylethanamines were prepared at close to theoretical yields by using Candida antarctica lipase B (Novozym 435) catalyzed ( R )‐selective N ‐acylation with isopropyl butanoate (enantiomeric ratio E > 200). The use of N ‐methyl‐2‐pyrrolidinone (NMP) as a cosolvent (1:30) in isopropyl butanoate solved the problem of low solubility of the compounds. Instability of the heterocyclic ring systems against traditional acid‐ and base‐catalyzed hydrolysis was solved by using Candida antarctica lipase A as a commercial CAL‐A‐CLEA preparation for deprotection of the N ‐acylated ( R ) enantiomers in water. The slow, highly enantioselective ( E > 200) hydrolyses of racemic butanamides was also observed in the presence of Novozym 435.

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