Abstract: A freshprepared solution of lithium tert-butoxide in DMF was used to replace solution of lithium tertbutoxide in THF for the deproton of hydroxyl group of (R)-9-(hydroxylpropyl) adenine, during the reaction between (R)-9-(hydroxylpropyl) adenine and diethyl p-toluenesulfonyloxymethyl phosphate. Thus, the reaction could be carried out more safely. In addition, the molar ratio of (R)-9-［2-(diethylphosphonomethoxy) propyl］ adenine to trimethylsilyl bromide initially set at 1∶6 for the removal of two ethyl groups in (R)-9［2-(diethylphosphonomethoxy) propyl］ adenine was changed to 1∶4.5. The product was characterized by 1H-NMR and mass spectral analysis, and the results show it is the same as that obtained by the original procedure.