Diastereoselective synthesis of the acid part of a new muscarinic M3 receptor antagonist

被引：21

作者：

Mitsuya, M ^{[1
]}

Ogino, Y ^{[1
]}

Ohtake, N ^{[1
]}

Mase, T ^{[1
]}

机构：

[1] Merck Res Labs, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

来源：

TETRAHEDRON | 2000年 / 56卷 / 51期

关键词：

muscarinic receptor; antagonist; Michael addition; enolate;

D O I：

10.1016/S0040-4020(00)00961-3

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Diastereoselective synthesis of (2R)-2-[(1R)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetic acid 1, an important component of a novel muscarinic M-3 receptor antagonist 3, was achieved via Michael addition of an enolate of chiral dioxolane 4 to (-)-dicyclopentadiene 9 in 90% de as a key step. The desired Michael adduct 10, which was easily isolated by recrystallization of a mixture of diastereomers, was submitted to retrograde Diels-Alder reaction. Subsequent hydrogenation of the resultant enone 12 gave the key intermediate 5 in 91% chemical yield from 10. (C) 2000 Elsevier Science Ltd. All rights reserved.

引用

页码：9901 / 9907

页数：7

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