One-Step Synthesis of 5-(4-Fluorobenzyl)-2-furyl Methyl Ketone:A Key Intermediate of HIV-lntegrase Inhibitor S-1360

摘要

Practical one-step synthesis of 5-(4-fluorobenzyl)-2-furyl methyl ketone was accomplished by Friedel-Crafts benzylation of 2-furyl methyl ketone with 4-fluorobenzyl chloride in the presence of ZnCl2.Two reaction conditions and their work-up procedures are reported.The first utilizes an anhydrous condition in dichlo-romethane,providing a convenient procedure for the isolation of the product.The second involves an aqueous condition,which offers a large-scale ecological and safe manufacturing process.