Practical Asymmetric Fluorination Approach to the Scalable Synthesis of New Fluoroaminothiazine BACE Inhibitors

Here we report an optimized protocol for the asymmetric introduction of a fluorine atom into a quaternary center facilitated by d-proline, Selectfluor®, and trifluoroethanol. The synthesis proceeds over four steps starting from a chiral amino alcohol precursor and provides the desired enantiomer wit...

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Bibliographic Details
Published inOrganic process research & development Vol. 22; no. 5; pp. 650 - 654
Main Authors Garcia-Losada, Pablo, Barberis, Mario, Shi, Yuan, Hembre, Erik, Alhambra Jimenez, Carolina, Winneroski, Leonard L, Watson, Brian M, Jones, Chauncey, DeBaillie, Amy C, Martínez-Olid, Francisco, Mergott, Dustin J
Format Journal Article
LanguageEnglish
Published American Chemical Society 18.05.2018
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Summary:Here we report an optimized protocol for the asymmetric introduction of a fluorine atom into a quaternary center facilitated by d-proline, Selectfluor®, and trifluoroethanol. The synthesis proceeds over four steps starting from a chiral amino alcohol precursor and provides the desired enantiomer with no erosion of chiral purity and good diastereoselectivity. The process optimization allowed diastereoselective preparation of the key intermediate on a multigram scale.
ISSN:1083-6160
1520-586X
DOI:10.1021/acs.oprd.8b00069