Ligandless Heck coupling between a halogenated aniline and acrylonitrile catalyzed by Pd/C: Development and optimization of an industrial-scale Heck process for the production of a pharmaceutical intermediate

被引：47

作者：

Schils, Didier ^{[1
]}

Stappers, Fred ^{[1
]}

Solberghe, Geoffrey ^{[1
]}

van Heck, Richard ^{[1
]}

Coppens, Nfichelle ^{[1
]}

Van den Heuvel, Dirk ^{[2
]}

Van der Donck, Peter ^{[3
]}

Callewaert, Tom ^{[3
]}

Meeussen, Frank ^{[3
]}

De Bie, Erika ^{[4
]}

Eersels, Kristof ^{[5
]}

Schouteden, Ellen ^{[5
]}

机构：

[1] Johnson & Johnson Pharmaceut Res & Dev, API Dev, Chem Proc Res, B-2340 Beerse, Belgium

[2] Johnson & Johnson Pharmaceut Res & Dev, API Dev, Chem Proc Control, B-2340 Beerse, Belgium

[3] Johnson & Johnson Pharmaceut Res & Dev, API Dev, Pilot Plant, B-2340 Beerse, Belgium

[4] Johnson & Johnson Pharmaceut Res & Dev, API Dev, Safety Testing Lab, B-2340 Beerse, Belgium

[5] Johnson & Johnson Pharmaceut Res & Dev, API Dev, Chem Prod, B-2340 Beerse, Belgium

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2008年 / 12卷 / 03期

关键词：

D O I：

10.1021/op8000383

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

The aniline derivative 3 is a key building block of rilpivirine (TMC278) 2, a new potent NNRTI compound under clinical evaluation. In this paper we describe the development of a new synthesis of 3 based on a Heck coupling between a halogenated aniline and acrylonitrile using low loading of Pd/C (0.5 mol %) as catalyst. This resulted in a process which has been successfully transferred into production on 2400 mol-scale (6000 L reactor)

引用

页码：530 / 536

页数：7

共 25 条

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