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

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...

Full description

Saved in:
Bibliographic Details
Published in:Organic process research & development 2008-05, Vol.12 (3), p.530-536
Main Authors: Schils, Didier, Stappers, Fred, Solberghe, Geoffrey, van Heck, Richard, Coppens, Michelle, Van den Heuvel, Dirk, Van der Donck, Peter, Callewaert, Tom, Meeussen, Frank, Bie, Erika De, Eersels, Kristof, Schouteden, Ellen
Format: Article
Language:English
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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)
ISSN:1083-6160
1520-586X
DOI:10.1021/op8000383