Scale-up Guide: Base Reaction

Scale-Up Guide: High-Throughput Base Screen

Important Note

To best enable scale-up success, the use of glove box is highly recommended. However, modified bench top techniques are provided below.

General Guidelines for 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

All solids (base, substrates, catalyst) were weighed on a bench top balance and added to a cooled, oven dried flask 1,2 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 removed 3 and the reaction allowed to stir at the required temperature for the duration of the reaction.

1 See the Cross-Coupling Reaction Manual: Desk Reference and Cross-Coupling Quick Guide: Bench Reference for more detailed additional guidance and troubleshooting tips

2 Reaction 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.

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

Mouse over image to select.

KitAlysis

 

 

 

Product No. Description Vial
RDD019 K3PO4 A1, C1
900501 K2CO3 A2, C2
791733 KOAc A3, C3
237205 KHCO3 A4, C4
757551 KOH A5, C5
795429 NaOH A6, C6
441902 Cs2CO3 B1, D1
225770 LiHMDS 1.0 M in THF B2, D2
702706 NaOtBu 2.0 M in THF B3, D3
139009 DBU B4, D4
900632 Et3N B5, D5
n/a Chemist’s Choice B6, D6

All contents in the foil bag are weighed, plated, packed, and sealed in a glove box under nitrogen.