The reaction of ethyl iminodiacetate (I) with 2-ethoxycarbonylacetyl chloride (II) by means ot triethylamine in refluxing methylene chloride gives ethyl N-(2-ethoxycarbonylacetyl)iminodiacetate (III), which is cyclized by means of sodium ethoxide in refluxing ethanol yielding ethyl 4-hydroxy-3-(ethoxycarbonyl)-DELTA3-pyrrolin-2-one-1-acetate (IV). The isomerization of (IV) with water in refluxing acetonitrile affords ethyl pyrrolidine-2,4-dione-1-acetate (V), which is reduced with NaBH4 in dimethoxyethane to ethyl 4-hydroxypyrrolidine-2-one-1-acetate (VI). Finally, this compound is treated with ammonia in methanol.
The silylation of 3-hydroxy-4-aminobutyric acid (VII) with bistrimethylsilyl amine gives 3-(trimethylsilyloxy)-4-aminobutyric acid (VIII), which is cyclized to 4-(trimethylsilyloxy)-2-pyrrolidinone (IX) by heating. The treatment of (IX) with ethyl bromoacetate (A) affords ethyl 4-(trimethylsilyloxy)pyrrolidine-2-one-1-acetate (X), which by desilylation with HCl gives ethyl 4-hydroxypyrrolidine-2-one-1-acetate (VI). Finally, this compound is treated with ammonia in methanol.