Improved Continuous Flow Processing: Benzimidazole Ring Formation via Catalytic Hydrogenation of an Aromatic Nitro Compound
Chemical Process Research and Development, Teva Pharmaceuticals, 383 Phoenixville Pike, Malvern, Pennsylvania 19355, United States
Org. Process Res. Dev., Article ASAP
Publication Date (Web): August 6, 2013 (Article)
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.