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An Improved Process for the Preparation of Tenofovir Disoproxil Fumarate

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journal contribution
posted on 04.03.2016, 00:00 by Darren L. Riley, David R. Walwyn, Chris D. Edlin
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.