合成路线1

The 9-[2-(phosphonomethoxy)ethyl]adenine (VIII), intermediate in the synthesis of adefovir has been obtained as follows: 1) The partial hydrolysis of 2-acetoxyethoxymethylphosphonic acid diethyl ester (I) with Dowex 50XB in ethanol gives the corresponding 2-hydroxyethoxymethylphosphonate (II), which is treated with CCl4/PPh3, with CBr4/PPh3 or with TsCl yielding 2-choroethoxy (III), 2-bromoethoxy (IV) or 2-tosyloxyethoxy (V) derivatives, respectively (1). The condensation of (III), (IV) or (V) with adenine (VI) by means of NaH in hot DMF affords 9-[2-(diethoxyphosphorylmethoxy)ethyl]adenine (VII), which is finally treated with TMS-Br in acetonitrile to give the desired intermediate 9-[2-(phosphonomethoxy)ethyl]adenine (VIII). 2) The condensation of N6-benzoyl-9-(2-hydroxyethyl)adenine (IX) with tosyloxymethylphosphonic acid dimethyl ester (X) by means of NaH in warm DMF gives 9-[2-(dimethoxyphosphorylmethoxy)ethyl]adenine (X), which is treated first with NaOH in DMF/water and finally with TMS-I in DMF to afford the desired intermediate 9-[2-(phosphonomethoxy)ethyl]adenine (VIII).