Preparation of the intermediate silver carboxylate salt (V) is by esterification of p-(chloromethyl)benzoic acid (I) employing diazomethane, followed by displacement of the chloro group by NaI-furnished iodo ester (III). Reaction of iodide (III) with silver dibenzyl phosphate produced phosphate ester (IV). The methyl ester group of (IV) was then hydrolyzed with LiOH and subsequently converted to the silver carboxylate salt by means of AgNO3.
Conversion of the known compound (VI) into the title prodrug is by the following procedure: Treatment of the potassium salt of (VI) with (chloromethyl) chloroformate (A) at -78 C gave the chloromethoxycarbonyl derivative (VII), which was further converted to the iodo analogue (VIII) under Finkelstein conditions. Compound (VIII) was then coupled with the silver carboxylate (V) in refluxing toluene to provide ester (IX). The benzyl ester groups of (IX) were deprotected by transfer hydrogenolysis, and the phosphoric acid derivative was finally treated with NaOH to yield the title sodium phosphate salt.