Synthesis of (R,S)-[2,3-13C2]-1-(1'-methyl-2'-pyrrolidinyl)propan-2-one; {(R,S)-[2',3'-13C2]hygrinePound right bracePound

2-Ethoxy-1-methyl-5-pyrrolidinone (1) was reacted with ethyl [3,4-13C2]-acetoacetate (2) in the presence of TiCl4 to give ethyl [3,4-13C2]-2-(1'-methyl-5'-oxo-2'-pyrrolidinyl)-3-oxobutanoate (3) in 85% yield. Decarboethoxylation of ethyl [3,4-13C2]-2-(1'-methyl-5'-oxo-2'-pyrrolidinyl)-3-oxobutan-oate (3) was accomplished using NaCl and H2O in DMSO to give (R,S)-[2,3-13C2]-1-(1'-methyl-5'-oxo-2'-pyrrolidinyl)propan-2-o ne (4) in 91% yield. Protection of the ketone as a ketal (ethylene glycol, H+), followed by reduction of the amide to the amine using LiAlH4 and subsequent deprotection of the ketal gave (R,S)-[2,3-13C2]-1-(1'-methyl-2'-pyrrolidinyl)propan-2-one ((R,s)-[2', 3'-13C2]Hygrine) (8) in 78% yield. (61% overall yield from ethyl [3,4-13C2]acetoacetate). (Author)