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Synthesis of Trifluoromethylated Analogues of 4,5‐Dihydroorotic Acid
Author(s) -
Sukach Volodymyr A.,
Resetnic Anastasia A.,
Tkachuk Viktor M.,
Lin Zhengguo,
Kortz Ulrich,
Vovk Mykhailo V.,
Röschenthaler GerdVolker
Publication year - 2015
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.201403495
Subject(s) - chemistry , enantiopure drug , hydrocyanation , trifluoromethyl , trimethylsilyl cyanide , steric effects , intramolecular force , stereochemistry , medicinal chemistry , tertiary amine , organic chemistry , enantioselective synthesis , catalysis , alkyl
4‐(Trifluoromethyl)pyrimidin‐2(1 H )‐ones react with trimethylsilyl cyanide in the presence of a tertiary amine catalyst to give Michael‐like 1,4‐conjugate hydrocyanation adducts exclusively at the 3,6‐positions. The resulting 2‐oxo‐6‐(trifluoromethyl)‐1,2,3,4‐tetrahydropyrimidine‐4‐carbonitriles have been used to synthesize new trifluoromethylated 4,5‐dihydroorotic acid analogues and their esters in racemic as well as enantiopure forms by a chiral auxiliary approach. The orthogonal intramolecular C–F ··· C=O interaction between the fluorine atom of the CF 3 group and the carbon atom of the ester group observed in the crystal state may stabilize the sterically unfavourable conformation of the methyl 2‐oxo‐6‐(trifluoromethyl)hexahydropyrimidine‐4‐carboxylate molecule with axially oriented substituents.