Process for the preparation of L-ribavirin

1. A process for the preparation of a compound of the formula (IV)

which consists of:

a) the reaction of a triazole of the formula

wherein R 2 is a C 1 -C 4 alkoxycarbonyl, arylalkoxycarbonyl, carboxyl, cyano, carboxyamide group

with a protected ribofuranose of the formula

wherein Pg represents a group protecting the hydroxyl function and R 1 represents a leaving group selected from the group consisting of C 1 -C 4 acyloxy, aryloxy, halogen, and mixtures thereof;

in the presence of from 1 to 1.5 moles of a Lewis acid for every mole of (II) and

of a solvent selected from the group consisting of a halogenated hydrocarbon, an ether, an aromatic hydrocarbon, and mixtures thereof having a reflux temperature,

said reaction step a) preformed at a reaction temperature between −10° C. and the reflux temperature of the solvent; and

b) the removal of the Pg groups and the conversion of the R 2 group of the compound obtained of the formula

wherein Pg and R 2 have the meanings given above, into a carboxyamide group, to give a compound of the formula (IV),

wherein the triazole (I), ribofuranose (II), and solvent are provided to the reaction step a) as a pre-cooled suspension and the Lewis acid is added to the pre-cooled suspsension while maintaining a temperature below 20° C.

2. A process according to claim 1 , wherein R 2 represents a C 1 -C 4 alkoxycarbonyl group.

3. A process according to claim 1 , wherein Pg is selected from the group consisting of acetyl, benzoyl, benzyl, and mixtures thereof.

4. A process according to claim 1 , wherein R 1 represents a group selected from group consisting of chlorine, bromine, C 1 -C 4 acyloxy, and mixtures thereof.

5. A process according to claim 1 , wherein the Lewis acid is selected from the group consisting of AlCl 3 , SbCl 5 , BF 3 , SnCl 4 , FeCl 3 , and mixtures thereof.

6. A process according to claim 1 wherein the solvent used in stage a) is a halogenated hydrocarbon.

7. A process according to claim 1 , wherein the reagents in stage a) are used in a molar ratio of 1-2 moles of formula (I) and 1-1.5 moles of Lewis acid to each mole of formula (II).

8. A process according to claim 1 , wherein the compound of formula (IV) is isolated by crystallisation from aqueous methanol.

9. A process according to claim 8 , wherein said crystallisation is carried out at a temperature below 50° C. and using from 2 to 5 volumes of methanol per volume of water.

10. A process according to claim 2 , wherein R 2 represents a carbomethoxy group.

11. A process according to claim 3 , wherein Pg represents acetyl.

12. A process according to claim 4 , wherein R 1 represents acetoxy.

13. A process according to claim 6 , wherein the Lewis acid is SnCl 4 .

14. A process according to claim 1 , wherein said halogenated hydrocarbon is dichloromethane.

15. A process for the preparation of a compound of the formula (IV)

which consists of:

a) the reaction of a triazole of the formula

wherein R 2 is a C 1 -C 4 alkoxycarbonyl, arylalkoxycarbonyl, carboxyl, cyano, carboxyainide group

with a protected ribofuranose of the formula

wherein Pg represents a group protecting the hydroxyl function and R 1 represents a leaving group selected from the group consisting of C 1 -C 4 acyloxy, aryloxy, halogen, and mixtures thereof;

in the presence of a Lewis acid selected from the group consisting of AlCl 3 , SbCl 5 , BF 3 , SnCl 4 FeCl 3 , and mixtures thereof and

a halogenated hydrocarbon solvent having a reflux temperature,

said reaction step a) performed at a reaction temperature between −10° C. and the reflux temperature of the solvent; and

b) the removal of the Pg groups and the conversion of the R 2 group of the compound obtained of the formula

wherein Pg and R 2 have the meanings given above, into a carboxyamide group, to give a compound of the formula (IV).

16. The process of claim 15 , wherein the solvent is an halogenated hydrocarbon selected from the group consisting of dichloromethane, chloroform, trichloroethane, and mixtures thereof.