Gyula Lukács

Lithiation of 2-(chloroaryl)-2-methyl-1,3-dioxolanes and application in synthesis of new Ortho-functionalized acetophenone derivatives

Abstract 2-(4-Chlorophenyl)-2-methyl-1,3-dioxolane 2a was lithiated ortho to the ketal group by treatment with butyllithium in THF at 0°C. Related 2-aryl-2-methyl-1,3-dioxolanes possessing a chlorine substituent at the meta position of the aryl group 2b , c were lithiated with butyllithium in THF at −78°C at the position between the two directing groups. The lithio species thus generated were treated with various electrophiles to give ortho -functionalized acetophenone derivatives.

Stereochemistry and enantiomeric purity of a novel anxiolytic agent, deramciclane fumarate

The synthesis, stereostructure, and enantiomeric separation by chromatography of a new, chiral anxiolytic agent, deramciclane fumarate (2, (-)-[1R,2S,4R]-2-(2-dimethylaminoethoxy)-2-phenyl-1,7, 7-trimethylbicyclo[2.2.1]heptane fumarate, EGIS-3886), is described. The optical antipode and the racemate of compound 2 were also prepared. The structure was determined by single crystal X-ray diffraction analysis. The enantiomeric separation was accomplished by HPLC on Chiralcel OD (250 x 4.6 mm; 10 microm) and hexane-ethanol (99.5:0.5) as mobile phase at room temperature. The enantiomeric purity of the synthesized drug substance proved to be very high (>99. 9%). Some statements published earlier on the stereostructure of deramciclane fumarate are critically discussed.