Synthesis of [4-3H]-2-pyrrolidinone, [4-3H]-N-methyl-2-pyrrolidinone and N-[14C-methyl]-2-pyrrolidinone

An efficient synthesis of 2‐pyrrolidinone and N‐methyl‐2‐pyrrolidinone was developed in which the compounds can be labeled with tritium at either the 3‐ and 4‐positions or the 4‐position of the lactam ring. Cyclization of [2,3‐3H]‐γ‐aminobutyric acid (GABA) yielded [3,4‐3H]‐2‐pyrrolidinone and cyclization of [3‐3H]‐GABA, prepared by acid‐catalyzed exchange of tritium from [2,3‐3H]‐GABA, yielded [4‐3H]‐2‐pyrrolidinone was synthesized by methylation of [3,4‐3H]‐2‐pyrrolidinone using phase transfer catalysis, followed by basecatalyzed tritium exchange. N‐[14C‐Methyl]‐2‐pyrrolidinone was prepared from [14C] methyl iodide and 2‐pyrrolidinone, also using phase transfer catalysis.