Patent ID: 8569490

Claim:
A method of preparing entecavir of formula (1), comprising the steps of (a) conducting olefination of an α-hydroxy ketone compound of formula (2) to obtain an exomethylene compound of formula (3); (b) carrying out a Mitsunobu reaction of the exomethylene compound of formula (3) with a purine derivative to obtain a nucleoside compound of formula (4); (c) removing the protecting groups of the nucleoside compound of formula (4) to obtain a compound of formula (5); and (d) hydrolyzing the compound of formula (5): wherein R 1 and R 2 are each independently H or a hydroxy-protecting group, or R 1 and R 2 are fused together to form a cyclic hydroxy-protecting group; R 3 is selected from the group consisting of H, alkylsilyl, and allylsilyl; and X is selected from the group consisting of chloro, iodo, and benzyloxy.