A facile synthesis of saxagliptin intermediate N-Boc-3-hydroxyadamantylglycine

A facile synthesis of saxagliptin intermediate N-Boc-3-hydroxyadamantylglycine Commercial-scale synthesis of (S)-N-Boc-3-hydroxyadamantylglycine (I), which is the key intermediate of saxagliptin, can be achieved from 2-(3-hydroxy-1-adamantyl)-2-oxoacetic acid (6) by reductive amination with phenylalanine dehydrogenase. The biological enzyme used in the original medicinal chemistry route is expensive and not easily obtained, making it unsuitable for further development. In this work, we developed a conventional chemical approach to give the corresponding oxime from oxoacetic acid followed by reduction of oxime and protected amino with (Boc)2O to afford the racemic mixture of N-Boc-3-hydroxyadamantylglycine (III). Utilizing this route, N-Boc-3-hydroxyadamantylglycine was prepared in six linear chemical steps with 38 % overall yield. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Research on Chemical Intermediates Springer Journals

A facile synthesis of saxagliptin intermediate N-Boc-3-hydroxyadamantylglycine

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Publisher
Springer Journals
Copyright
Copyright © 2014 by Springer Science+Business Media Dordrecht
Subject
Chemistry; Catalysis; Physical Chemistry; Inorganic Chemistry
ISSN
0922-6168
eISSN
1568-5675
D.O.I.
10.1007/s11164-013-1515-3
Publisher site
See Article on Publisher Site

Abstract

Commercial-scale synthesis of (S)-N-Boc-3-hydroxyadamantylglycine (I), which is the key intermediate of saxagliptin, can be achieved from 2-(3-hydroxy-1-adamantyl)-2-oxoacetic acid (6) by reductive amination with phenylalanine dehydrogenase. The biological enzyme used in the original medicinal chemistry route is expensive and not easily obtained, making it unsuitable for further development. In this work, we developed a conventional chemical approach to give the corresponding oxime from oxoacetic acid followed by reduction of oxime and protected amino with (Boc)2O to afford the racemic mixture of N-Boc-3-hydroxyadamantylglycine (III). Utilizing this route, N-Boc-3-hydroxyadamantylglycine was prepared in six linear chemical steps with 38 % overall yield.

Journal

Research on Chemical IntermediatesSpringer Journals

Published: Jan 11, 2014

References

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