Process for preparing Ezetimibe intermediate by an acid enhanced chemo- and enantioselective CBS catalyzed ketone reduction

被引：41

作者：

Fu, XY ^{[1
]}

McAllister, TL ^{[1
]}

Thiruvengadam, TK ^{[1
]}

Tann, CH ^{[1
]}

Su, D ^{[1
]}

机构：

[1] Schering Plough Corp, Inst Res, Dept Synthet Chem, Union, NJ 07083 USA

来源：

TETRAHEDRON LETTERS | 2003年 / 44卷 / 04期

关键词：

ezetimibe; R-MeCBS; asymmetric ketone reduction;

D O I：

10.1016/S0040-4039(02)02700-4

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The S alcohol in the benzylic position of compound 2, a key feature of a novel cholesterol lowering agent Ezetimibe, was introduced by the (R)-MeCBS catalyzed asymmetric carbonyl reduction of ketone 1 using borane tetrahydrofuran complex (BTHF) as the reducing agent. The chemo- and enantioselectivity was dramatically enhanced by using an acid as a scavenger of the stabilizer sodium borchydride present in the commercially supplied pure BTHF. The effect of the critical reaction parameters such as addition mode of reagent, temperature, acids as well as water content on the selectivity has been examined. This reaction has been successfully applied in the commercial process for the preparation of the key intermediate 2 for Ezetimibe. (C) 2003 Elsevier Science Ltd. All rights reserved.

引用

页码：801 / 804

页数：4

共 18 条

[11] Synthesis of 3-arylpropenyl, 3-arylpropynyl and 3-arylpropyl 2-azetidinones as cholesterol absorption inhibitors: Application of the palladium-catalyzed arylation of alkenes and alkynes
Rosenblum, SB
Huynh, T
Afonso, A
Davis, HR
[J]. TETRAHEDRON, 2000, 56 (31) : 5735 - 5742
[12] Discovery of 1-(4-fluorophenyl)-(3R)-[3-(4-fluorophenyl)-(3S)-hydroxypropyl]-(4S)-(4-hydroxyphenyl)-2-azetidinone (SCH 58235):: A designed, potent, orally active inhibitor of cholesterol absorption
Rosenblum, SB
Huynh, T
Afonso, A
Davis, HR
Yumibe, N
Clader, JW
Burnett, DA
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (06) : 973 - 980
[13] Highly enantioselective reduction of prochiral ketones with N,N-diethylaniline center dot borane (DEANB) in oxazaborolidine-catalyzed reductions
Salunkhe, AM
Burkhardt, ER
[J]. TETRAHEDRON LETTERS, 1997, 38 (09) : 1523 - 1526
[14] AN IMPROVED METHOD FOR CHIRAL OXAZABOROLIDINE-CATALYZED REDUCTION OF 4-CHROMANONE ANALOGS AND MK-0499
SHI, YJ
CAI, DW
DOLLING, UH
DOUGLAS, AW
TSCHAEN, DM
VERHOEVEN, TR
[J]. TETRAHEDRON LETTERS, 1994, 35 (35) : 6409 - 6412
[15] VanHeek M, 1997, J PHARMACOL EXP THER, V283, P157
[16] A novel one-step diastereo- and enantioselective formation of trans-azetidinones and its application to the total synthesis of cholesterol absorption inhibitors
Wu, GZ
Wong, YS
Chen, X
Ding, ZX
[J]. JOURNAL OF ORGANIC CHEMISTRY, 1999, 64 (10) : 3714 - 3718
[17] Enzymatic glucuronidation of a novel cholesterol absorption inhibitor, SCH 58235
Zaks, A
Dodds, DR
[J]. APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY, 1998, 73 (2-3) : 205 - 214
[18] In situ NMR study of asymmetric borane reduction reaction - an abnormal factor in the temperature effect on the bis-oxazaborolidine catalyst and the relationship between the catalyst structure and selectivity
Zhao, JK
Bao, XH
Liu, XM
Wan, BS
Han, XW
Yang, CG
Hang, JF
Feng, Y
Jiang, B
[J]. TETRAHEDRON-ASYMMETRY, 2000, 11 (16) : 3351 - 3359

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