In the development of a new route to the synthesis of bendamustine hydrochloride, the API of Trenda�, a key intermediate was generated via reduction of an aromatic nitro compound by catalytic hydrogenation. The reaction process was optimized and scaled up successfully to make kilograms of product in a pressurized batch reactor. Because of safety concerns, limits on the scale of batch reactor, and additional expense and time for outsourcing, a continuous flow hydrogenation for the reaction was investigated using the H-cube�, a commercially available flow reactor. Scale-up of the process was developed and demonstrated successfully on the H-cube Midi�. The flow process eliminated the safety concerns associated with hydrogen gas and pyrophoric catalyst. The product was generated at kilogram scale with yields and purity comparable to the batch process.

Catalytic hydrogenation of an aromatic nitro compound: From batch to continuous flow processing

244th National Meeting (2012)

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