An improved synthesis of 4-aminobutanenitrile from 4-azidobutanenitrile and comments on room temperature stability
Date
2021
Authors
Capon, P.K.
Avery, T.D.
Purdey, M.S.
Abell, A.D.
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Synthetic Communications, 2021; 51(3):428-436
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Patrick K. Capon, Thomas D. Avery, Malcolm S. Purdey and Andrew D. Abell
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Abstract
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. 1H-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 °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 °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.
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