Synthesis of a Library of N-Substituted Methyl Aminocarbonyl Acetates using Poly(Ethylene Glycol) as Soluble Support

A rapid and solvent-free synthesis of methyl 2-(N-substituted aminocarbonyl) acetates has been developed using poly (ethylene glycol) (PEG) as a soluble polymeric support and as a protecting group. PEG was first reacted with Meldrum's acid to give PEG-bound malonic acid 2 under microwave-irradiation, and then 2 was coupled with series of amines to produce 3, followed by the cleavage from the PEG using KCN in CH3OH to afford N-substituted methyl aminocarbonyl acetates 4. This simple method requires mild reaction conditions and affords moderate to high yields of the desired products with excellent purities.