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.
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Acknowledgments
This work was supported by the Natural Science Foundation of Chongqing (CSTC, 2006BB5286). We furthermore thank Chongqing Medical University for partial financial support of this work. We are grateful to Yue Feng and Jun Pen for helpful discussions related to this work.
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Chen, Y., Wang, A., Tao, Z. et al. A facile synthesis of saxagliptin intermediate N-Boc-3-hydroxyadamantylglycine. Res Chem Intermed 41, 4113–4121 (2015). https://doi.org/10.1007/s11164-013-1515-3
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DOI: https://doi.org/10.1007/s11164-013-1515-3