The Large-Scale Synthesis of (S)‑N‑Boc-bis(4-fluorophenyl)alanine
The synthesis of (S)-N-Boc-bis(4-fluorophenyl)alanine, an intermediate in the synthesis of denagliptin, is described from the synthesis of a 12 g proof of principle sample to a >900 kg cGMP manufacturing campaign. The chiral centre was established by the asymmetric hydrogenation of the sterically...
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| Veröffentlicht in: | Organic process research & development 2013-01, Vol.17 (1), p.69-76 |
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| container_title | Organic process research & development |
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| creator | Appell, Robert B Boulton, Lee T Daugs, Edward D Hansen, Matt Hanson, Christopher H Heinrich, Jerry Kronig, Christel Lloyd, Richard C Louks, David Nitz, Mark Praquin, Céline Ramsden, James A Samuel, Helen Smit, Mark Willets, Matthew |
| description | The synthesis of (S)-N-Boc-bis(4-fluorophenyl)alanine, an intermediate in the synthesis of denagliptin, is described from the synthesis of a 12 g proof of principle sample to a >900 kg cGMP manufacturing campaign. The chiral centre was established by the asymmetric hydrogenation of the sterically crowded precursor, ethyl 2-acetamido-3,3-bis(4-fluorophenyl)acrylate. The ability to isolate the various intermediates in a physical form that would readily allow filtration, washing, and ultimately purification underpinned the successful manufacturing campaign. |
| doi_str_mv | 10.1021/op3002855 |
| format | Article |
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| title | The Large-Scale Synthesis of (S)‑N‑Boc-bis(4-fluorophenyl)alanine |
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