Reaction #554635

ord-5596620960c34ab1b1f43852351e4fcd

Reaction equation

COc1ccc2c(c1)CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](O)C=C[C@@H]12
3-methoxy-17β-hydroxyestra-1,3,5(10),15-tetraene
c1ccc(P(c2ccccc2)c2ccccc2)cc1
triphenylphosphine
O=C(O)c1ccc([N+](=O)[O-])cc1
4-nitrobenzoic acid
CC(C)OC(=O)N=NC(=O)OC(C)C
diisopropyl azodicarboxylate
[Cl-].[Na+]
sodium chloride
→
COc1ccc2c(c1)CC[C@@H]1[C@@H]2CC[C@]2(C)C(OC(=O)c3ccc([N+](=O)[O-])cc3)C=C[C@@H]12
title compound
Yield 78.5%
COc1ccc2c(c1)CC[C@@H]1[C@@H]2CC[C@]2(C)C(OC(=O)c3ccc([N+](=O)[O-])cc3)C=C[C@@H]12
3-Methoxy-estra-1,3,5(10),15-tetraen-17-yl 4-nitrobenzoate
Yield 78.5%

Reactants

COc1ccc2c(c1)CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](O)C=C[C@@H]12
3-methoxy-17β-hydroxyestra-1,3,5(10),15-tetraene
c1ccc(P(c2ccccc2)c2ccccc2)cc1
triphenylphosphine
O=C(O)c1ccc([N+](=O)[O-])cc1
4-nitrobenzoic acid
CC(C)OC(=O)N=NC(=O)OC(C)C
diisopropyl azodicarboxylate
[Cl-].[Na+]
sodium chloride

Reagents

None

Solvents

C1CCOC1
tetrahydrofuran

Conditions

Temperature
23°CELSIUS
Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    Extractionextracted with ethyl acetate
  2. 2
    Washthe combined organic extracts are washed with saturated sodium chloride solution
  3. 3
    Dryingdried over sodium sulfate
  4. 4
    OtherThe residue obtained
  5. 5
    Filtrationafter filtration and solvent removal
  6. 6
    workup.ADDITIONtreated with 80 ml of a 30% hydrogen peroxide solution
  7. 7
    Temperaturewith cooling
  8. 8
    workup.ADDITIONafter 20 minutes poured
  9. 9
    Temperaturewith cooling into 600 ml of a semi-concentrated sodium thiosulfate solution
  10. 10
    ExtractionThis is extracted with ethyl acetate
  11. 11
    Washthe combined organic extracts are washed with saturated sodium chloride solution
  12. 12
    Dryingdried over sodium sulfate
  13. 13
    OtherThe residue obtained
  14. 14
    Filtrationafter filtration and solvent removal
  15. 15
    Otheris purified by recrystallisation

Procedure

The solution of 43.9 g of 3-methoxy-17β-hydroxyestra-1,3,5(10),15-tetraene in 1.61 tetrahydrofuran is treated with 121 g of triphenylphosphine, 27.1 g of 4-nitrobenzoic acid and 30.9 ml of diisopropyl azodicarboxylate and stirred at 23° C. for 2 hours. This is treated with saturated sodium chloride solution, extracted with ethyl acetate, and the combined organic extracts are washed with saturated sodium chloride solution and dried over sodium sulfate. The residue obtained after filtration and solvent removal is taken up 1.2 l acetone, treated with 80 ml of a 30% hydrogen peroxide solution with cooling, and after 20 minutes poured with cooling into 600 ml of a semi-concentrated sodium thiosulfate solution. This is extracted with ethyl acetate, and the combined organic extracts are washed with saturated sodium chloride solution and dried over sodium sulfate. The residue obtained after filtration and solvent removal is purified by recrystallisation. 52.5 g of the title compound are isolated.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08623850B2uspto-grants-2014_01