Nitration Chemistry in Continuous Flow using Fuming Nitric Acid in a Commercially Available Flow Reactor

• Cara E. Brocklehurst
• Hansjoerg Lehmann
• Luigi La Vecchia

• Global Discovery Chemistry, Novartis, Basel, Switzerland

The paper will describe the use of flow chemistry for scaling up exothermic or hazardous nitration reactions. Such reactions often cause time delays to the delivery of larger batches of intermediates or final compounds for medicinal chemistry projects, because considerable time is required for safety evaluation and, if necessary, modification of the procedure so that it can be scaled-up and run in a safe manner. A commercially available continuous flow reactor was used in the scale up of three challenging nitrations including a reaction involving a potentially explosive mixture of acetic acid and fuming nitric acid, with a productivity of 97 g/h.

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