Adipic Acid → Adipic anhydride

Participants

Reaction Steps

Rapamycin 42-ester with adipic acid was prepared by a variation of the method of Example 2. Adipic anhydride was prepared by combining 146 mg adipic acid in 1.0 mL dimethylformamide with 200 μL dicyclohexylcarbodiimide and incubating at room temperature 2h. 300 μL of the supernatant of this reaction was added to 90 mg rapamycin and 45 mg dimethylaminopyridine dissolved in 200 μL methylene chloride. After 5 min the mixture was centrifuged to sediment precipitated material. The supernatant was partitioned between 3 mL water with 100 μL acetic acid and 2×1 mL methylene chloride. The organic layers were combined, dried with anhydrous sodium sulfate and the solvent evaporated. The residue was dissolved in 1.0 mL methanol and 0.5 mL ethanol, cooled in ice, and precipitated by adding 5 mL water. This was centrifuged, the supernatant discarded and the residue dried in a vacuum desiccator, yielding 78 mg white powder.

Provenance & Evidence