A single-step, one-pot process to obtain zotarolimus and other rapamycinderivatives on large scale that improves currently available syntheses. In oneembodiment, dried rapamycin is dissolved in isopropylacetate . After coolingand 2,6-Lutidine addition, triflic anhydride is slowly added at -30~ C. Saltsare removed by filtration. Tetrazole, followed by a tert-basediisopropylethylamine is added. After incubation at room temperature, theproduct is concentrated and purified by a silica gel column using THF/heptaneas eluant. The product is collected, concentrated, and purified using anacetone/heptane column. The product-containing fractions are concentrated. Theproduct is dissolved in t-BME and precipitated with heptane. The solids aredissolved in acetone, treated with butylated-hydroxy toluene, and the solutionconcentrated. The process is repeated twice with acetone to remove solvents.At least one stabilizing agent is added, such as BHT at 0.5% before drying.
