Improved Asymmetric Synthesis of 3,4-Dihydro-2-[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-5-[3-(trifluorometho xy)phenyl]-alpha-(trifluoromethyl)-1(2H)-quinolineethanol, a Potent Cholesteryl Ester Transfer Protein Inhibitor

摘要

The asymmetric synthesis of 3,4-dihydro-2-[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-5-[3-(trifluorometho xy)phenyl]-alpha-(trifluoromethyl)-1(2h)-quinolineethanol (compound 11), a cholesteryl ester transfer protein Inhibitor, is accomplished. The asymmetric center is established via the chiral reduction of ketone 4 employing Corey's (R)-Me CBS oxazaborolidine reagent, The tetrahydroquinoline core of the molecule is established via a Cu-mediated intramolecular amination reaction. The preparation of the prochiral ketone 4 has also been improved by eliminating the use of a hazardous aryltin reagent.