Stereoretentive Etherification of an α‑Aryl-β-amino Alcohol Using a Selective Aziridinium Ring Opening for the Synthesis of AZD7594
A selective aziridinium ring-opening was used to etherify an α-aryl-β-amino alcohol with stereochemical retention. This transformation was achieved in a biphasic system to address phenoxide solubility and the formation of a sulfonate ester impurity. The protecting group strategy was directed by a st...
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| Veröffentlicht in: | Journal of organic chemistry 2019-04, Vol.84 (8), p.4629-4638 |
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| container_end_page | 4638 |
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| container_issue | 8 |
| container_start_page | 4629 |
| container_title | Journal of organic chemistry |
| container_volume | 84 |
| creator | McMillan, Angus E Steven, Alan Ashworth, Ian W Mullen, Alexander K Chan, Lai C Galan Espinosa, Maria Rita Pilling, Michael J Raw, Steven A Jones, Martin F |
| description | A selective aziridinium ring-opening was used to etherify an α-aryl-β-amino alcohol with stereochemical retention. This transformation was achieved in a biphasic system to address phenoxide solubility and the formation of a sulfonate ester impurity. The protecting group strategy was directed by a stability study of the activated α-aryl-β-amino alcohol in this system. Process analytical techniques were used to establish reaction understanding, and mixing on large scale was modeled in silico. The process provided a selective and efficient method of preparing the nonsteroidal, inhaled selective glucocorticoid receptor modulator AZD7594. |
| doi_str_mv | 10.1021/acs.joc.8b01062 |
| format | Article |
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| language | eng |
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| source | ACS Publications |
| title | Stereoretentive Etherification of an α‑Aryl-β-amino Alcohol Using a Selective Aziridinium Ring Opening for the Synthesis of AZD7594 |
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