Réaction #554635

ord-5596620960c34ab1b1f43852351e4fcd

Équation de réaction

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
Rendement 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
Rendement 78.5%

Réactifs

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

Réactifs

Aucun

Solvants

C1CCOC1
tetrahydrofuran

Conditions de réaction

Température
23°CELSIUS
Conditions détaillées
See reaction.notes.procedure_details.

Traitement

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

Mode opératoire

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.v1Brevet: US08623850B2uspto-grants-2014_01