The present manuscript describes a simple, two step synthesis of tenofovir from HPA through phosphonomethalation with a novel doubly protected oxymethylphosphonate electrophile. The crystalline electrophile can be prepared in a simple reaction sequence and can be deblocked more easily than its ditehyl analogue involved in the current commercial process for making the drug.
The approach is general and can also be used for the preparation of related antivirals and the synthesis of adefovir is described as well.
Version Sep 15, 2020
SI Tenofovir ChemRxiv