Synthesis of Tegafur by the Alkylation of 5-Fluorouracil under the Lewis Acid and Metal Salt-Free Conditions

Abstract

A novel protocol for preparation of tegafur (a prodrug of 5-fluorouracil) is reported. The process involves the 1,8-diazabicycloundec-7-ene-mediated alkylation of 5-fluorouracil with 2-acetoxytetrahydrofuran at 90 °C, followed by treatment of the prepurified mixture of the alkylation products with aqueous ethanol at 70 °C. The yield of the two-step process is 72%.