Synthesis of the Neurotransmitter 4-Aminobutanoic Acid (GABA) from Diethyl Cyanomalonate

GABA was synthesized by deethoxycarbonylation, ester hydrolysis and nitrile reduction of a highly functionalized intermediate obtained by alkylation of diethyl cyanomalonate with ethyl bromoacetate. By judicious employment of D2O or NaBD4 in one of the three functional group transformation steps, deuterium was selectively introduced into each of the three possible sites in GABA.