Synthesis of a NO-releasing prodrug of rofecoxib

被引：30

作者：

Engelhardt, FC ^{[1
]}

Shi, YJ ^{[1
]}

Cowden, CJ ^{[1
]}

Conlon, DA ^{[1
]}

Pipik, B ^{[1
]}

Zhou, G ^{[1
]}

McNamara, JM ^{[1
]}

Dolling, UH ^{[1
]}

机构：

[1] Merck & Co Inc, Dept Process Res, Rahway, NJ 07065 USA

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2006年 / 71卷 / 02期

关键词：

D O I：

10.1021/jo051712g

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A newly developed synthesis of a NO-releasing prodrug of rofecoxib is described. The highly productive process consists of five chemical steps and produces prodrug 1 in an overall 64% yield from commercially available 3-phenyl-2-propyn-1-ol (4). The synthesis is highlighted by the carbometalation reaction of propargyl alcohol 4 to generate the tetrasubstituted olefin core, sulfone acid 2. Additionally, two alternate end-game strategies to prepare NO-COXIB I from this intermediate were explored and developed: (1) a convergent synthesis where a bromonitrate side chain is introduced in one step and (2) a two-step sequence that first installs the requisite six-carbon ester side chain followed by chemoselective nitration.

引用

页码：480 / 491

页数：12

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