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Improved asymmetric synthesis route delivers a potent tetrahydroquinoline CETP inhibitor without a hazardous aryltin reagent (Org Lett 2009)

Original title: Improved asymmetric synthesis of 3,4-dihydro-2-[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-5-[3-(trifluoromethoxy)phenyl]-alpha-(trifluoromethyl)-1(2H)-quinolineethanol, a potent cholesteryl ester transfer protein inhibitor

Org Lett · · 4

Rano TA, Kuo GH

Chemists report an improved asymmetric synthesis of compound 11, a potent cholesteryl ester transfer protein inhibitor with a tetrahydroquinoline core. The asymmetric center is established through chiral reduction of a ketone intermediate using Corey's (R)-Me CBS oxazaborolidine reagent, and the tetrahydroquinoline ring is built via a copper-mediated intramolecular amination reaction. The route also improves preparation of the prochiral ketone precursor by eliminating a hazardous aryltin reagent used in earlier syntheses, a practical advance for scaling production of this CETP inhibitor class.

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Original abstract

The asymmetric synthesis of 3,4-dihydro-2-[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-5-[3-(trifluoromethoxy)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.

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Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.