An Improved Process for the Preparation of Tenofovir Disoproxil Fumarate

The current three-step manufacturing route for the preparation of tenofovir disoproxil fumarate (1) was assessed and optimized leading to a higher yielding, simpler, and greener process. Key improvements in the process route include the refinement of the second stage through the replacement of the p...

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Published inOrganic process research & development Vol. 20; no. 4; pp. 742 - 750
Main Authors Riley, Darren L, Walwyn, David R, Edlin, Chris D
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 15.04.2016
Amer Chemical Soc
Subjects
Chemistry
Chemistry, Applied
Chemistry, Organic
Physical Sciences
Science & Technology
IN-VITRO
PMPA
PHARMACOKINETICS
PRODRUG
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Summary:The current three-step manufacturing route for the preparation of tenofovir disoproxil fumarate (1) was assessed and optimized leading to a higher yielding, simpler, and greener process. Key improvements in the process route include the refinement of the second stage through the replacement of the problematic magnesium tert-butoxide (MTB) with a 1:1 ratio of a Grignard reagent and tert-butanol. The development of a virtually solvent-free approach and the establishment of a workup and purification protocol which allows the isolation of a pure diethyl phosphonate ester (8) was achieved.
ISSN:1083-6160
1520-586X
DOI:10.1021/acs.oprd.5b00364