Di- tert -butyl Phosphonate Route to the Antiviral Drug Tenofovir
© 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...
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| Format: | Article |
| Language: | English |
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American Chemical Society (ACS)
2022
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| Online Access: | https://hdl.handle.net/1721.1/141083 |
| _version_ | 1826209152176750592 |
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| author | Dietz, Jule-Philipp Ferenc, Dorota Jamison, Timothy F Gupton, B Frank Opatz, Till |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Dietz, Jule-Philipp Ferenc, Dorota Jamison, Timothy F Gupton, B Frank Opatz, Till |
| author_sort | Dietz, Jule-Philipp |
| collection | MIT |
| description | © 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). |
| first_indexed | 2024-09-23T14:18:20Z |
| format | Article |
| id | mit-1721.1/141083 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:18:20Z |
| publishDate | 2022 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1410832023-04-13T16:06:49Z Di- tert -butyl Phosphonate Route to the Antiviral Drug Tenofovir Dietz, Jule-Philipp Ferenc, Dorota Jamison, Timothy F Gupton, B Frank Opatz, Till Massachusetts Institute of Technology. Department of Chemistry © 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). 2022-03-09T15:36:30Z 2022-03-09T15:36:30Z 2021 2022-03-09T15:33:34Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/141083 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). en 10.1021/ACS.OPRD.0C00473 Organic Process Research and Development Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Chemical Society (ACS) chemRxiv |
| spellingShingle | Dietz, Jule-Philipp Ferenc, Dorota Jamison, Timothy F Gupton, B Frank Opatz, Till Di- tert -butyl Phosphonate Route to the Antiviral Drug Tenofovir |
| title | Di- tert -butyl Phosphonate Route to the Antiviral Drug Tenofovir |
| title_full | Di- tert -butyl Phosphonate Route to the Antiviral Drug Tenofovir |
| title_fullStr | Di- tert -butyl Phosphonate Route to the Antiviral Drug Tenofovir |
| title_full_unstemmed | Di- tert -butyl Phosphonate Route to the Antiviral Drug Tenofovir |
| title_short | Di- tert -butyl Phosphonate Route to the Antiviral Drug Tenofovir |
| title_sort | di tert butyl phosphonate route to the antiviral drug tenofovir |
| url | https://hdl.handle.net/1721.1/141083 |
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