Chemoenzymatic Preparation of 1‐Heteroarylethanamines of Low Solubility

• 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

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.