IMPROVED CONTINUOUS FLOW PROCESSING: BENZIMIDAZOLE RING FORMATION VIA CATALYTIC HYDROGENATION OF AN AROMATIC NITRO COMPOUND

 

 

http://pubs.acs.org/doi/full/10.1021/op400179f

Org. Process Res. Dev., 2014, 18 (11), pp 1427–1433

DOI: 10.1021/op400179f

Jian Chen, Katrin Przyuski, Renee Roemmele, and Roger P. Bakale

pp 1427–1433

Publication Date (Web): August 6, 2013 (Article)

DOI: 10.1021/op400179f

In the development of a new route to bendamustine hydrochloride, the API in Treanda, the key benzimidazole intermediate 5 was generated via catalytic heterogeneous hydrogenation of an aromatic nitro compound using a batch reactor. Because of safety concerns and a site limitation on hydrogenation at scale, a continuous flow hydrogenation for the reaction was investigated at lab scale using the commercially available H-Cube. The process was then scaled successfully, generating kilogram quantities on the H-Cube Midi. This flow process eliminated the safety concerns about the use of hydrogen gas and pyrophoric catalysts and also showed 1200-fold increase in space–time yield versus the batch processing.

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