Practical Synthesis of Methyl Z-2-(N-Acetylamino) but-2-Enoate. An Intermediate to D- and L-2-Aminobutyric Acid

Abstract

Treatment of inexpensive L- or DL-threonine methyl ester with acetic anhydride and either pyridine or anhydrous sodium acetate at reflux results in dehydration yielding the N,N-diacetamide of the title compound in >80% yield. Monodeacetylation of the diacetamide with 0.1 equiv of triethylamine in methanol affords the title monoacetamido derivative 1 in nearly quantitative yield.

Notes

Differences in the dehydration of serine and threonine may result from threonine having to adopt a conformation where the methyl group must be syn-periplanar to a large group for elimination to occur thus incurring a substantial non-bonded interaction as the reaction proceeds through the transition state.