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...
Published in: | European Journal of Organic Chemistry |
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Main Authors: | , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Wiley
2012
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Subjects: | |
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 |
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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