Production method for adefovir dipivoxil
The present invention relates to an improved method of preparing adefovir dipivoxil of Formula 1. The method of the present invention is characterized by using dimethylsulfoxide as a reaction solvent, and comprises a process of preparing adefovir dipivoxil of Formula 1 by allowing adefovir of Formula 2 to react with chloromethylpivalate at a reaction temperature of 30 to 50° C. under the presence of dimethylsulfoxide and triethylamine solvents.
1. A method of preparing adefovir dipivoxil of Formula 1, comprising the step of reacting adefovir of Formula 2 with chloromethylpivalate under the presence of dimethylsulfoxide and triethylamine solvents:
2. The method of claim 1 , wherein the prepared adefovir dipivoxil of Formula 1 contains 15% or less of byproducts of Formula 3:
3. The method of claim 1 , wherein the reaction is carried out at a temperature of 30 to 50° C.
4. The method of any one of claims 1 to 3 , wherein the reaction is carried out for 3 to 7 hours.
5. The method of any one of claims 1 to 3 , further comprising the step of purifying the prepared adefovir dipivoxil of Formula 1.
6. The method of claim 5 , wherein the purification step comprises the steps of dissolving the prepared adefovir dipivoxil of Formula 1 in water or a water-containing mixed solvent; purifying the adefovir dipivoxil solution through a reverse-phase column of which a stationary phase is hydrophobic; adding an organic solvent to the purified adefovir dipivoxil solution; and adding a base to the organic solvent-added solution.
7. The method of claim 6 , wherein the water-containing mixed solvent is a solvent in which water is dissolved in one or more solvents selected from the group consisting of C1 to C4 alcohol, acetone, acetonitrile, tetrahydrofuran, and dioxane in a concentration of 20 wt % or higher.