Scale-Up Guide: Copper C-N Cross-Coupling Reaction

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Important Note

All of the catalysts used in the kit are sensitive to air and moisture in their commercially available form. Please see the catalyst MSDS or product detail page for details on handling and storage. To best enable scale-up success, the use of glove box is highly recommended. However, modified bench top techniques are provide below.

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)
  • Use unopened Sure/Seal™ anhydrous solvents (or newly degassed)
  • Keep reactions under an atmosphere of nitrogen
  • Purge needle/syringe with nitrogen prior to use

Example Experimental-Glovebox Set-up, hood reaction

The olefin substrate was weighed on a bench top balance and added to a cooled, oven dried flask equipped with an oven dried stir bar. The reaction was capped and then transferred standard chemical glove box. Once in the glove box, anhydrous SureSeal™ solvent was added via syringe. If use of acid additive was desired, this was added to the olefin solution. The catalyst (removed from the glove box fridge or brought in the box from a bench fridge) was then weighed and added to the reaction mixture, the mixture capped, and then removed from the glove box. Upon arrival at the bench, a reflux condenser, fitted with a septa and connected to a nitrogen-fed manifold needle (to allow the safe escape of ethylene without the loss of solvent while keeping the reaction under inertion) was connected to the reaction flask. The reaction was then added to a pre-heated oil bath and allowed to stir at the required temperature for the duration of the reaction.

Example Experimental-Bench Top set-up, hood reaction

The olefin substrate was weighed on a bench top balance and added to a cooled, oven dried two-neck flask equipped with an oven dried stir bar. A reflux condenser, fitted with a septa and connected to a nitrogen-fed manifold needle (to allow the safe escape of ethylene without the loss of solvent was attached to the vertical neck of the flask and the other neck was fitted with a septa. The reaction set-up was then evacuated and backfilled with nitrogen (3x, making sure to allow time as the set-up is larger than a single reaction flask). Anhydrous solvent (SureSeal™ed and punctured with a nitrogen-fed manifold needle) was then added via syringe. If use of acid additive was desired, this was added to the olefin solution via syringe through the septa. The catalyst was removed from the fridge, quickly weighed and then added to the reaction by opening the septa for a short interval. (A stock solution of the catalyst in a portion of the reaction solvent can also be used to add the catalyst via syringe or cannula). The reaction was then allowed to stir at the required temperature for the duration of the reaction. The catalyst bottle was flushed with nitrogen and placed back in the fridge for storage.

Copper Cu-CN Cross-Coupling Reaction Product List

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Description Product No. Vial
2,6-Dimethylanilino(oxo)acetic acid 806412 A1, B1, C1, D1
2,6-Dimethoxyanilino(oxo)acetic acid
806455
A2, B2, C2, D2
2,6-Difluoroanilino(oxo)acetic acid 806439 A3, B3, C3, D3
2,3,4,5,6-Pentafluoroanilino(oxo)acetic acid 806447 A4, B4, C4, D4
3,5-Bis(trifluoromethyl)anilino(oxo)acetic acid
806420
A5, B5, C5, D5
2-Fluoro-6-(piperidine-1-sulfonyl)anilino(oxo)acetic acid
805491
A6, B6,C6, D6

 

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