Synthesis and purification of valacyclovir

A method of making N-tert-butoxycarbonyl-L-valine 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy] ethyl ester comprising the step of coupling N-t-butoxycarbonyl valine with acyclovir in the presence of a coupling agent.

A method of making valacyclovir or a pharmaceutically acceptable salt thereof comprising the steps of:

• coupling an amine protected valine selected from N-t-butoxycarbonyl valine and N-formyl valine with acyclovir to form a protected valacyclovir, and
• deprotecting the protected valacyclovir to form valacyclovir or a pharmaceutically acceptable salt thereof.

A method of making valacyclovir hydrochloride comprising the steps of:

• coupling an amine protected valine selected from N-t-butoxycarbonyl valine and N-formyl valine with acyclovir to form a protected valacyclovir, wherein the coupling is effected with a coupling agent selected from N-(3-dimethylaminopropyl)-N-ethyl carbodiimide and dicyclohexylcarbodiimide, and
• deprotecting the protected valacyclovir with hydrochloric acid.

A method of making valacyclovir hydrochloride in pure form comprising the steps of:

• forming a slurry of valacyclovir hydrochloride in a lower alkyl alcohol,
• refluxing the slurry, and
• isolating pure valacyclovir hydrochloride from the slurry.

A method of making valacyclovir hydrochloride in pure form comprising the steps of:

• forming a solution of valacyclovir hydrochloride in water,
• mixing the solution with isopropanol to form a slurry, and
• isolating valacyclovir hydrochloride in pure form from the slurry.

Valacyclovir hydrochloride in pure form.