合成路线1

A new synthetic route to famciclovir has been described: The alkylation of 2,2-dimethyl-1,3-dioxan-5-one (I) with vinylmagnesium bromide (II) in THF gives the 2,2-dimethyl-5-vinyl-1,3-dioxan-5-ol derivative (II), which is treated with methyl chloroformate in the same solvent to yield the mixed carbonate (IV). Condensation of (IV) with 6-chloropurine-2-amine (V) by means of 1,2-bis(diphenylphosphino)ethane (dppe) and tris(dibenzylideneacetone)dipalladium(0) [Pd2(dba)3] in DMF at 80 °C for 7.5 h affords a 5:95 mixture of the N-7 (VI) and N-9 (VII) regioisomers, respectively. Hydrogenation of regioisomer (VII) with H2 over Pd/C in THF eliminates the 6-chlorine atom and reduces the exocyclic double bond giving the 2-aminopurine derivative (VIII), which is treated with HCl in methanol to remove the acetonide group affording diol (IX). Finally, this compound is acylated with acetic anhydride and DMAP/TEA in dichloromethane.