A single-step, one-pot process to obtain zotarolimus and other rapamycinderivatives on largescale that improves currently available syntheses. In one embodiment, driedrapamycin isdissolved in isopropylacetate. After cooling and 2,6-Lutidine addition,triflic anhydride is slowlyadded at -30°C. Salts are removed by filtration. Tetrazole, followed bya tert-basediisopropylethylamine is added. After incubation at room temperature, theproduct isconcentrated and purified by a silica gel column using THF/heptane as eluant.The product iscollected, concentrated, and purified using a heptane/acetone column. Theproduct-containingfractions are concentrated. The product is dissolved in .tau.-BME andprecipitated with heptane.The solids are dissolved in acetone, treated with butylated-hydroxy toluene,and the solutionconcentrated. The process is repeated twice with acetone to remove solvents.At least onestabilizing agent is added, such as BHT at 0.5% before drying.
