Synthesis ofN‐Acetyl‐α‐aminobutyric AcidviaAmidocarbonylation: A Case Study

Abstract
The synthesis ofN‐acetyl‐α‐aminobutyric acid by amidocarbonylation of propionaldehyde with acetamide in the presence of palladium catalysts is studied in detail. The influence of various reaction conditions and compositions (e.g., the co‐catalysts acid and bromide) on the yield ofN‐acetyl‐α‐aminobutyric acid is shown. For the first time it is demonstrated that the palladium‐catalyzed amidocarbonylations of aldehydes can be run with significantly lower halide concentrations (<30 mol %) without a major yield decrease. While phosphine‐free catalyst systems give best yields at low CO pressure, phosphine‐ligated palladium catalysts lead to better yields at higher CO pressure. At low palladium loadings (<0.1 mol %), unwanted condensation reactions of propionaldehyde become increasingly competitive.

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