Adipic Acid → Adipic anhydride

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.

1. waitAfter 5 min the mixture was centrifuged
2. customto sediment precipitated material
3. customThe supernatant was partitioned between 3 mL water with 100 μL acetic acid and 2×1 mL methylene chloride
4. dry with materialdried with anhydrous sodium sulfate
5. customthe solvent evaporated
6. dissolutionThe residue was dissolved in 1.0 mL methanol
7. temperature0.5 mL ethanol, cooled in ice
8. customprecipitated
9. additionby adding 5 mL water
10. customthe residue dried in a vacuum desiccator

ORDレコード

ord-68d1606a060f473bb06bdb49ca15d1a1

出典データセット

uspto-grants-2003_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06541612B2