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J Org Chem. 2018 Jul 3. doi: 10.1021/acs.joc.8b01062. [Epub ahead of print]

Stereoretentive Etherification of an α-Aryl-β-amino Alcohol Using a Selective Aziridinium Ring Opening for the Synthesis of AZD7594.

Author information

1
Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences , ETH Zürich , 8093 Zürich , Switzerland.
2
Global Chemical Development, Pharmaceutical Development , AstraZeneca , Macclesfield Campus , Macclesfield SK10 2NA , U.K.

Abstract

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.

PMID:
29920203
DOI:
10.1021/acs.joc.8b01062

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