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

被引：24

作者：

Rano, Thomas A. ^{[1
]}

Kuo, Gee-Hong ^{[1
]}

机构：

[1] Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ 08869 USA

来源：

ORGANIC LETTERS | 2009年 / 11卷 / 13期

关键词：

REDUCTION; DESIGN; AMINES;

D O I：

10.1021/ol900639j

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

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.

引用

页码：2812 / 2815

页数：4

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