Di- tert -butyl Phosphonate Route to the Antiviral Drug Tenofovir
Name
the-di-tert-butyl-oxymethylphosphonate-route-to-the-antiviral-drug-tenofovir.pdf
Description
Submitted version
Size
1 MB
Format
Adobe PDF
Checksum (MD5)
9a672c7b692f62a4cec392b9aa5c67ea
Author(s)
Dietz, Jule-Philipp
Ferenc, Dorota
Jamison, Timothy F
Gupton, B Frank
Opatz, Till
Date Issued
2021
Journal
Organic Process Research and Development
Publisher
American Chemical Society (ACS)
Citation
Dietz, Jule-Philipp, Ferenc, Dorota, Jamison, Timothy F, Gupton, B Frank and Opatz, Till. 2021. "Di- tert -butyl Phosphonate Route to the Antiviral Drug Tenofovir." Organic Process Research and Development, 25 (4).
Version
Original manuscript
Abstract
© Di-tert-butyl oxymethyl phosphonates were investigated regarding their suitability for preparing the active pharmaceutical ingredient tenofovir (PMPA). First, an efficient and simple access to the crystalline di-tert-butyl(hydroxymethyl)phosphonate was developed. O-Mesylation gave high yields of the active phosphonomethylation reagent. For the synthesis of tenofovir, a two-step sequence was developed using Mg(OtBu)2 as the base for the alkylation of (R)-9-(2-hydroxypropyl)adenine. Subsequent deprotection could be achieved with aqueous acids. (Di-tert-butoxyphosphoryl)methyl methanesulfonate showed to be the most efficient electrophile tested, affording PMPA in 72% yield on a 5 g scale. The developed protocol could also be applied for the preparation of the hepatitis B drug adefovir (64% yield/1 g scale).
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1021/ACS.OPRD.0C00473
