C14-Labelled Synthesis of Benalaxyl-M and Its Two Soil Metabolites

The radiosynthesis of the systemic fungicide for oomycete disease control Benalaxyl-M and its two most relevant soil metabolites was developed from the versatile common [phenyl-U-¹⁴C]N-(2,6-dimethylphenyl)-D-alanine methyl ester intermediate 4 by reaction with Meldrum's acid and subsequent hydrolysis of the ester group. The triflate of the methyl ester of (S)-lactic acid 6 employed in the synthesis of [phenyl-U-14C]N-(2,6-dimethylphenyl)-D-alanine methyl ester allows us an optimal use of the labelled [phenyl-U-14C]2,6-dimethylaniline. The greater reactivity of the triflate of the methyl ester of (S)-lactic acid compared to the analogous p-toluenesulfonate or methanesulfonate allows the reaction to occur at room temperature with higher enantiomeric purity and better yield.