Reaction #342987

ord-02d98f1c2f7c48a680b8802981bcbaa0

Reaction equation

CC[C@@]1(O)C(=O)OCc2c1cc1n(c2=O)Cc2cc3ccccc3nc2-1
Camptothecin
O=S(=O)(O)O
sulfuric acid
CO.ClC(Cl)Cl
methanol chloroform
O=S(=O)([O-])OOS(=O)(=O)[O-].[NH4+].[NH4+]
ammonium persulfate
→
CC[C@@]1(O)C(=O)OCc2c1cc1n(c2=O)Cc2c-1nc1ccccc1c2CO
7-hydroxymethylcamptothecin

Reactants

—
ice water
CC[C@@]1(O)C(=O)OCc2c1cc1n(c2=O)Cc2cc3ccccc3nc2-1
Camptothecin
O=S(=O)(O)O
sulfuric acid
CO.ClC(Cl)Cl
methanol chloroform
O=S(=O)([O-])OOS(=O)(=O)[O-].[NH4+].[NH4+]
ammonium persulfate

Reagents

None

Solvents

CO
methanol

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    workup.DISSOLUTIONdissolved
  2. 2
    workup.ADDITIONby addition under ice-
  3. 3
    workup.ADDITIONTo the solution was added dropwise
  4. 4
    Temperatureunder reflux
  5. 5
    Extractionthe organic matter was extracted with a mixture (1:1, 500 ml) of dioxane-chloroform
  6. 6
    Dryingdried with anhydrous magnesium sulfate
  7. 7
    Filtrationfiltered
  8. 8
    Otherevaporated until dryness under reduced pressure
  9. 9
    Temperaturewas warmed (50°-60° C.) with methanol (200 ml)
  10. 10
    FiltrationAn insoluble matter was collected by filtration
  11. 11
    Otherdried under reduced pressure
  12. 12
    Otherrecrystallized from dimethylformamide-dioxane whereupon 40 mg (36.9%) of 7-hydroxymethylcamptothecin
  13. 13
    Otherwere obtained as light yellow white prismatic crystals

Procedure

Camptothecin (100 mg, 0.287 m-mol) was suspended in methanol (25 ml) and then dissolved therein by addition under ice-cooling of 75% sulfuric acid (10 ml). To the solution was added dropwise under reflux with stirring an aqueous solution (100 ml) of ammonium persulfate (15 g, 0.0657 mol) over 16 hours. The reaction mixture was poured into ice water (100 ml) and the organic matter was extracted with a mixture (1:1, 500 ml) of dioxane-chloroform and then thrice with chloroform (100 ml×3). The organic phases were combined, dried with anhydrous magnesium sulfate, filtered and then evaporated until dryness under reduced pressure. The remaining solid having an orange color was warmed (50°-60° C.) with methanol (200 ml) and stirred for 30 minutes. An insoluble matter was collected by filtration, dried under reduced pressure and recrystallized from dimethylformamide-dioxane whereupon 40 mg (36.9%) of 7-hydroxymethylcamptothecin were obtained as light yellow white prismatic crystals having a melting point of 274°- 276° C. (dec.). Rf value 0.125 (5% methanol-chloroform).

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: USRE032518uspto-grants-1987_10