Synthesis of N-methyl 3-alkyl-isothiazolidine- 1,1-dioxo-3-methylcarboxylates through the intramolecular Michael reaction
DOI:
https://doi.org/10.15407/dopovidi2022.06.073Keywords:
sulfonamides, amino acids, cyclization, the Michael additionAbstract
An efficient and common method for the synthesis of N-methyl 3-alkyl-isothiazolidine-1,1-dioxo-3-methylcarboxylates has been developed. Readily available 2-monosubstituted β-amino acid esters hydrochlorides and β-chloroethylsulfonyl chloride were used as starting reagents. Methyl 2-alkyl-2-(vinylsulfonamido)ethanoates obtained on the first step were alkylated at the Nitrogen atom and converted into methyl 2-alkyl-2-(N-methylvinylsulfonamido) ethanoates. The latter were subjected to NaH-mediated intramolecular Michael addition thus affording the target methyl 3-alkyl-isothiazolidine-1,1-dioxo-3-methylcarboxylates. This class of compounds is considered as sulfonamide bioisostere of natural pyroglutamic acid (pGlu) and thus can be used in the synthesis of compounds with potential biological activity.
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