Di-tert-butyl dicarbonate → 17beta-Carbomethoxy-6-t-butoxycarbonyl-6-azaandrost-4-en-3-one

HRID 726132Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 726132
[C:1]([C@H:5]1[CH2:10][CH2:9][C@H:8]2[C@H:11]3[C@H:21]([CH2:22][CH2:23][C@:6]12[CH3:7])[C@:19]1([CH3:20])[C:14]([CH2:15][C@@H:16]([O:24][Si](C(C)C)(C(C)C)C(C)C)[CH2:17][CH2:18]1)=[N:13][CH2:12]3)([O:3][CH3:4])=[O:2].[C:35]([O:39][C:40](OC(OC(C)(C)C)=O)=[O:41])([CH3:38])([CH3:37])[CH3:36].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=O.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1>N1C=CC=CC=1.O1CCCC1.O>[C:1]([C@H:5]1[CH2:10][CH2:9][C@H:8]2[C@H:11]3[C@H:21]([CH2:22][CH2:23][C@:6]12[CH3:7])[C@:19]1([CH3:20])[C:14](=[CH:15][C:16](=[O:24])[CH2:17][CH2:18]1)[N:13]([C:40]([O:39][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:41])[CH2:12]3)([O:3][CH3:4])=[O:2]

Komponenten

8

Edukt 4

HCID 90495Di-tert-butyl dicarbonateHCID 2724130Cornforth reagentHCID 2724141Tetrabutylammonium FluorideHCID 1045826517beta-Carbomethoxy-3beta-triisopropylsilyloxy-6-azaandrost-5-ene

Produkt 1

HCID 1000287217beta-Carbomethoxy-6-t-butoxycarbonyl-6-azaandrost-4-en-3-one

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 1049PyridineLösungsmittel2×HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A portion of the crude product from above, 17β-carbomethoxy-3β-triisopropylsilyloxy-6-azaandrost-5-ene (66 g, 0.135 mol) is dissolved in pyridine (500 mL), treated with di-t-butyldicarbonate (150 g, 0.69 mol) and allowed to stir overnight. The pyridine is removed by rotary evaporation and tetrabutylammonium fluoride (500 mL, 1M, 0.5 mol) in tetrahydrofuran (THF) added carefully and the reaction heated to reflux for 5 min. The THF is removed by rotary evaporation, the residue dissolved in ethyl acetate (500 mL), washed cautiously with water, saturated aqueous NaCl, dried with MgSO4 and concentrated. This material is dissolved in DMF (500 mL), is treated with pyridinium dichromate (153 g, 0.41 mol) and allowed to stir overnight. The reaction is poured into water (700 mL) and extracted with ethyl acetate (2×500 mL). The combined extracts are washed with water, 5% aqueous CuSO4, saturated aqueous NaCl, dried over MgSO4, concentrated and flash chromatographed (0-60%, diethyl ether/hexanes) to give 17β-carbomethoxy-6-t-butoxycarbonyl-6-azaandrost-4-en-3-one as an off-white foam; yield: 37.5 g (64%); FAB mass spec. MH+ 432.

Aufarbeitung

  1. additionadded carefully
  2. temperaturethe reaction heated
  3. temperatureto reflux for 5 min
  4. customThe THF is removed by rotary evaporation
  5. dissolutionthe residue dissolved in ethyl acetate (500 mL)
  6. washwashed cautiously with water, saturated aqueous NaCl
  7. dry with materialdried with MgSO4
  8. concentrationconcentrated
  9. dissolutionThis material is dissolved in DMF (500 mL)
  10. stirringto stir overnight
  11. extractionextracted with ethyl acetate (2×500 mL)
  12. washThe combined extracts are washed with water, 5% aqueous CuSO4, saturated aqueous NaCl
  13. dry with materialdried over MgSO4
  14. concentrationconcentrated
  15. customflash chromatographed (0-60%, diethyl ether/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-8fcc3e4503b640be8e42532b82060868
Quelldatensatz
uspto-grants-1998_01
Patentnummer
US05708001

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