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Optimization of the Ugi Reaction Using Parallel Synthesis and Automated Liquid Handling
Journal article   Open access   Peer reviewed

Optimization of the Ugi Reaction Using Parallel Synthesis and Automated Liquid Handling

Jean-Claude Bradley, Khalid Baig Mirza, Tom Osborne, Antony Wiliams and Kevin Owens
Journal of Visualized Experiments, (21)
2008
PMID: 19066532
url
https://doi.org/10.3791/942View
Published, Version of Record (VoR) Open

Abstract

Chemistry
The optimization of a Ugi reaction involving the mixing of furfurylamine, benzaldehyde, boc-glycine and t-butylisocyanide is described. Triplicate runs of 48 parallel experiments are reported, varying concentration, solvent and the excess of some of the reagents. The isolation of the product was achieved by a simple filtration and wash procedure. The highest yield obtained was 66% from 0.4 M methanol with 1.2 eq. of imine. This is significantly above the 49% yield obtained from the initial reaction under equimolar concentration at 0.4 M in methanol. Methanol solutions with reagent concentrations of 0.4M or 0.2M gave superior yields while all solvent systems at 0.07M performed poorly. At 0.2M, methanol and ethanol/methanol (60/40) mixtures were statistically equally good while THF/methanol (60/40) was poor and acetonitrile/methanol (60/40) was intermediate. Good reproducibility of the precipitate yields was obtained in these replicate experiments, allowing for subtle interaction effects to be positively identified.

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