Synthesis of (R,S)-[2,3-C-13(2)]-1-(1'-methyl-2'-pyrrolidinyl)propan-2-one; {(R,S)-[2',3'-C-13(2)]hygrine}

2-Ethoxy-1-methyl-5-pyrrolidinone (1) was reacted with ethyl [3,4-C-13(2)]-acetoacetate (2) in the presence of TiCl4 to give ethyl [3,4-C-13(2)]-2-(1'-methyl-5'-oxo-2'-pyrrolidinyl)-3-oxobutanoate (3) in 85% yield. Decarboethoxylation of ethyl [3,4-C-13(2)]-2-(1'-methyl-5'-oxo-2'-pyrrolidinyl)-3-oxobutanoate (3) was accomplished using NaCl and H2O in DMSO to give (R,S)-[2,3-C-13(2)]-1-(1'-methyl-5'-oxo-2'-pyrrolidinyl)prop an-2-one (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-C-13(2)]-1-(1'-methyl-2'-pyrrolidinyl)propan-2-one ((R,S)-[2',3'-C-13(2)]Hygrine) (8) in 78% yield. (61% overall yield from ethyl [3,4-C-13(2)]acetoacetate).