Scale-Up Guide: Buchwald-Hartwig Amination

Kit to Hit Scale-Up Guide

Important Note

All of the preformed catalysts used in the kit are air and moisture stable complexes in their commercially available form. Once activated by base under the reaction conditions they become sensitive to air. To best enable scale-up success, the use of standard Schlenk technique is recommended.

General Guidelines for Catalytic Reaction Scale-Up

• Oven dry all glassware and stir bars
• Preheat oil bath to avoid temperature spiking
• Use dry, high purity reagents (and substrates)¹
• Use unopened Sure/Seal™ anhydrous solvents (or newly degassed)¹
• Keep reactions under an atmosphere of nitrogen

Example Experimental

All solids (base, substrates, catalyst) were weighed on a bench top balance and added to a cooled, oven dried flask¹ equipped with an oven dried stir bar. The reaction was capped and then purged and backfilled with nitrogen (3x) with a nitrogen-fed manifold needle. Anhydrous solvent (SureSeal™ed and punctured with a nitrogen-fed manifold needle) was then added via syringe.  If a liquid bases was required, it was added as the final component via syringe. When all constituents were added, the nitrogen line was removed² and the reaction allowed to stir at the required temperature for the duration of the reaction.

¹Reaction vials capable of being sealed with a microwave cap are very useful as well. By design, the caps do not need to be replaced once punctured.

²For higher temps, a reflux condenser operated under nitrogen can be used