Patent ID: 7968703

Claim:
A process for producing crystalline (−)-cis-2-hydroxymethyl-4-(cytosin-1′-yl)-1,3-oxathiolane comprising: a) reacting cis-2-hydroxymethyl-4-(cytosin-1′-yl)-1,3-oxathiolane with a chiral acid and an achiral acid to produce a diastereomeric salt and an a enantiomeric salt, wherein said chiral acid is (1R)-(−)-10-camphorsulfonic acid, and the reaction produces a chiral acid salt which is a mixture of (−)-cis-2-hydroxymethyl-4-(cytosin-1′-yl)-1,3-oxathiolane•(1R)-(−)-10-camphorsulfonic acid and (+)-cis-2-hydroxymethyl-4-(cytosin-1′-yl)-1,3-oxathiolane•(1R)-(−)-10-camphorsulfonic acid and (+)-cis-2-hydroxymethyl-4-(cytosin-1′-yl)-1,3-oxathiolane•(1R)-(−)-10-camphorsulfonic acid, wherein cis-2-hydroxymethyl-4-(cytosin-1′-yl)-1,3-oxathiolane is reacted with a half quantity molar amount of (1R)-(−)-10-camphorsulfonic acid, said molar amount being with regard to cis-2-hydroxymethyl-4-(cytosin-1′-yl)-1,3-oxathiolane; b) recovering said (−)-cis-2-hydroxymethyl-4-(cytosin-1′-yl)-1,3-oxathiolane•(1R)-(−)-10-camphorsulfonic acid; and c) converting said (−)-cis-2-hydroxymethyl-4-(cytosin-1′-yl)-1,3-oxathiolane•(1R)-(−)-10-camphorsulfonic acid into said crystalline (−)-cis-2-hydroxymethyl-4-(cytosin-1′-yl)-1,3-oxathiolane; wherein a) is performed in the presence of an aqueous/organic solvent mixture, and the overall yield of (−)-cis-2-hydroxymethyl-4-(cytosin-1′-yl)-1,3-oxathiolane is at least 25%.