The title compound was obtained from 3'-azido-3'-deoxythymidine (I) either by treatment with tri-n-butylammonium phosphite and DCC in pyridine or by treatment with phosphorus trichloride in the presence of imidazole and Et3N in acetonitrile or in the presence of triethyl phosphate, followed by aqueous hydrolysis.

3'-azido-3'-deoxythimidine (II) was phosphitylated with phosphorus trichloride in triethyl phosphate to yield the corresponding hydrogen phosphonate (III). Subsequent coupling of (III) with 1,2-dipalmitoylglycerol (IV) by means of pivaloyl chloride in pyridine produced phosphite ester (V), which was finally oxidized to the title phosphate with ethanolic iodine.

The synthesis of the title compound has been reported by two procedures. Coupling of dipalmitoylphosphatidic acid (I) to 3'-azido-3'-deoxythimidine (AZT) (II) was carried out using triisopropylbenzenesulfonyl chloride in pyridine to provide the target phosphate diester.