Reaction #640610

ord-7efd57db705e42b4904f203238bd83f2

Reaction equation

CC[C@]1(O)C[C@@H]2CN(CCc3c([nH]c4ccccc34)[C@@](C(=O)OC)(c3cc4c(cc3OC)N(C)[C@H]3[C@@](O)(C(=O)OC)[C@H](OC(C)=O)[C@]5(CC)C=CCN6CC[C@]43[C@@H]65)C2)C1.O=S(=O)(O)O
Vinblastine sulfate
CC[C@]1(O)C[C@@H]2CN(CCc3c([nH]c4ccccc34)[C@@](C(=O)OC)(c3cc4c(cc3OC)N(C)[C@H]3[C@@](O)(C(=O)OC)[C@H](OC(C)=O)[C@]5(CC)C=CCN6CC[C@]43[C@@H]65)C2)C1.O=S(=O)(O)O
vinblastine sulfate
O=C([O-])[O-].[Na+].[Na+]
sodium carbonate
→
CC[C@]1(O)C[C@@H]2CN(CCc3c([nH]c4ccccc34)[C@@](C(=O)OC)(c3cc4c(cc3OC)N(C)[C@H]3[C@@](O)(C(=O)OC)[C@H](OC(C)=O)[C@]5(CC)C=CCN6CC[C@]43[C@@H]65)C2)C1
vinblastine
Yield 97.0%

Reactants

CC[C@]1(O)C[C@@H]2CN(CCc3c([nH]c4ccccc34)[C@@](C(=O)OC)(c3cc4c(cc3OC)N(C)[C@H]3[C@@](O)(C(=O)OC)[C@H](OC(C)=O)[C@]5(CC)C=CCN6CC[C@]43[C@@H]65)C2)C1.O=S(=O)(O)O
Vinblastine sulfate
CC[C@]1(O)C[C@@H]2CN(CCc3c([nH]c4ccccc34)[C@@](C(=O)OC)(c3cc4c(cc3OC)N(C)[C@H]3[C@@](O)(C(=O)OC)[C@H](OC(C)=O)[C@]5(CC)C=CCN6CC[C@]43[C@@H]65)C2)C1.O=S(=O)(O)O
vinblastine sulfate
O=C([O-])[O-].[Na+].[Na+]
sodium carbonate

Reagents

None

Solvents

ClCCl
dichloromethane

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    OtherThe organic layer was separated
  2. 2
    Extractionaqueous solution was extracted with dichloromethane (2×20 mL)
  3. 3
    DryingThe combined organic layer and extracts were dried over sodium sulfate
  4. 4
    Otherevaporated to dryness

Procedure

Vinblastine sulfate was purchased from Asian Talent. A 610-mg sample of vinblastine sulfate was dissolved in 20 mL of dichloromethane and then it was shaken with 20 mL of 5% aqueous sodium carbonate. The organic layer was separated and aqueous solution was extracted with dichloromethane (2×20 mL) and then with chloroform (20 mL). The combined organic layer and extracts were dried over sodium sulfate and evaporated to dryness, affording 526 mg (97%) of vinblastine free base as a sticky white solid. The purity of vinblastine free base was checked by 1H 300 MHz NMR and HPLC (99.1% AUC) using a Varian CHROMSEP HPLC column SS 250×4.6 mm including holder with guard column, MICROSORB 100-5 C18; gradient: 30/70 (0.1% trifluoroacetic acid in acetonitrile)/(0.1% trifluoroacetic acid in water) to 100/0 (0.1% trifluoroacetic acid in acetonitrile)/(0.1% trifluoroacetic acid in water); detection at 254 nm and 270 nm.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08048872B2uspto-grants-2011_11