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Chemoenzymatic Preparation of 1‐Heteroarylethanamines of Low Solubility
Author(s) -
Brem Jürgen,
Bencze LászlóCsaba,
Liljeblad Arto,
Turcu Mihaela C.,
Paizs Csaba,
Irimie FlorinDan,
Kanerva Liisa T.
Publication year - 2012
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201200330
Subject(s) - chemistry , candida antarctica , enantioselective synthesis , enantiomer , acylation , hydrolysis , solubility , organic chemistry , isopropyl , kinetic resolution , benzofuran , lipase , enantiomeric excess , catalysis , enzyme
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.