An Improved Synthesis Of 4-Aminobutanenitrile From 4-Azidobutanenitrile And Comments On Room Temperature Stability

4-Aminobutanenitrile (1) is an important synthetic intermediate for neurological disorder therapeutics including Parkinson's and Alzheimer's diseases, and is an industrial precursor to pyrroline and pyrrolidine. Synthesis of 1 by Co(II) catalyzed reduction of 4-azidobutanenitrile (2) with NaBH4, or by a one-pot Staudinger reduction of 2 in THF, was low yielding. H-1-NMR analysis of the Staudinger reduction revealed the formation of iminophosphorane intermediate (3) after 22 h at rt, and that increasing the reaction temperature from rt to 40 degrees C promoted hydrolysis of 3 to 1. A modified Staudinger reduction of 2 involving pyridine as solvent, addition of water 3 h after triphenylphosphine, and a temperature increase to 40 degrees C, gave rise to 1 in 69% yield. 1 is unstable at rt, thus the hydrochloride salt of 1 (1.HCl) was prepared by bubbling HCl(g) through a solution of 1 in chloroform. 1.HCl is stable at rt and is hence the preferred form for storage.