Patent ID: 7595390

Claim:
An industrially scalable process for preparing a mixture of α-L-2′-deoxycytidine and β-L-2′-deoxycytidine or a mixture of α-L-thymidine and β-L-thymidine or a pharmaceutically acceptable salt thereof, comprising the steps of: (a) reacting an N- and/or O-protected cytosine or thymine with a silylating reagent at a temperature from about 10° C. to 50° C., or at ambient temperature, optionally in the presence of a catalyst, to form a silylated cytosine or thymine; (b) raising the temperature to reflux in order to run the reaction to completion; (c) cooling the mixture of (a) to about 0° C. to −20° C.; (d) reacting the silylated cytosine or thymine with a protected 1-halo-2-deoxy-L-sugar in the presence of a Lewis acid at a temperature of about 20° C. to form an N- and/or O-protected deoxycytidine or thymidine mixture; (e) reacting the N- and/or O-protected deoxycytidine or thymidine anomeric mixture with a deprotecting reagent, to form a mixture of α-L-2′-deoxycytidine and β-L-2′-deoxycytidine or a mixture of α-L-thymidine and β-L-thymidine, wherein the Lewis acid is selected from SnCl 4 , TiCl 4 , AlCl 3 , ZnCl 2 , CuII, SbCl 5 , and BF 3 (OEt 2 ), wherein said sugar moiety is a protected 2-deoxy-1-L-ribofuranosyl moiety, and wherein the predominate product in each product mixture is the β anomer.