Riley, Darren LyallWalwyn, David RichardEdlin, Chris D.2016-06-212016-04Riley, DL, Walwyn, DR & Edlin, CD 2016, 'An improved process for the preparation of tenofovir disoproxil fumarate', Organic Process Research and Development, vol. 20, no. 4, pp. 742-750.1083-6160 (print)1520-586X (online)10.1021/acs.oprd.5b00364http://hdl.handle.net/2263/53278The 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 work-up and purification protocol which allows the isolation of a pure diethyl phosphonate ester (8).enThis document is the Accepted Manuscript version of a Published Work that appeared in final form in Organic Process Research and Development, © 2016 American Chemical Society after peer review and technical editing by the publisher.TenofovirTenofovir disoproxil fumarateManufacturing routeProcess routeAn improved process for the preparation of tenofovir disoproxil fumaratePostprint Article