N,N-Dimethyl-1,3-propanediamine → N-[3-(Dimethylamino)propyl]-3-methoxyestra-1,3,5(10)-trien-17beta-amine

HRID 327918

Reaktionsgleichung

Reaktionsgleichung von HRID 327918
[CH3:1][C@@:2]12[C:10](=O)[CH2:9][CH2:8][C@H:7]1[C@@H:6]1[CH2:12][CH2:13][C:14]3[CH:19]=[C:18]([O:20][CH3:21])[CH:17]=[CH:16][C:15]=3[C@H:5]1[CH2:4][CH2:3]2.[CH3:22][N:23]([CH3:28])[CH2:24][CH2:25][CH2:26][NH2:27]>C(O)=O>[CH3:22][N:23]([CH3:28])[CH2:24][CH2:25][CH2:26][NH:27][C@H:10]1[CH2:9][CH2:8][C@H:7]2[C@H:6]3[C@H:5]([CH2:4][CH2:3][C@:2]12[CH3:1])[C:15]1[CH:16]=[CH:17][C:18]([O:20][CH3:21])=[CH:19][C:14]=1[CH2:13][CH2:12]3

Komponenten

4

Edukt 2

HCID 7993N,N-Dimethyl-1,3-propanediamineHCID 92895(+)-Estrone 3-methyl ether

Produkt 1

HCID 22849576N-[3-(Dimethylamino)propyl]-3-methoxyestra-1,3,5(10)-trien-17beta-amine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 284Formic AcidLösungsmittel

Versuchsvorschrift

Formic acid (97-98%, 47.5 ml) is added dropwise to a cooled and stiffed mixture of estrone methyl ether (71.0 g) and 3-dimethylaminopropylamine (158 ml). The resulting mixture is heated in an oil bath (165°-175° C.) for 20 hours. The reaction is quenched in ice water (total volume 700 ml) and the resulting alkaline (pH--9) mixture is extracted twice with CH2Cl2. The combined extracts are washed with dilute aq. NAOH and with brine, dried (Na2SO4), filtered, and concentrated, Hexane (250 ml) is added to the residue and a white fluffy precipitate is filtered off, The solvent is removed, leaving a residual light brown oil which slowly crystallizes. A portion (20 g) of this material is chromatographed over silica gel (500 g) packed as a slurry in 7.5% of 10% NH4OH--CH3OH in CH2Cl2. The column is eluted (300 ml fractions) with the same solvent system. The desired material (about 14 g) is eluted in fractions 13-26 and pooled in CH2Cl2. As this solution stands at 20°-25°, crystals form. After two days, the crystals (4.803 g), mp 184°-192° C. with rapid heating, are collected by filtration. More crystals form in the filtrate and after 3 days these are collected. The compound can be recrystallized from methanol-acetone in the freezer, giving the second title compound as crystals, mp 184°-186° C. decomposition (dec) with bubbling.

Aufarbeitung

  1. temperaturea cooled
  2. temperatureThe resulting mixture is heated in an oil bath (165°-175° C.) for 20 hours
  3. customThe reaction is quenched in ice water (total volume 700 ml)
  4. extractionthe resulting alkaline (pH--9) mixture is extracted twice with CH2Cl2
  5. washThe combined extracts are washed with dilute aq. NAOH and with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. additionHexane (250 ml) is added to the residue
  10. filtrationa white fluffy precipitate is filtered off
  11. customThe solvent is removed
  12. customleaving a residual light brown oil which
  13. customslowly crystallizes
  14. customA portion (20 g) of this material is chromatographed over silica gel (500 g)
  15. washThe column is eluted (300 ml fractions) with the same solvent system
  16. washThe desired material (about 14 g) is eluted in fractions 13-26
  17. customstands at 20°-25°
  18. customcrystals form
  19. filtrationthe crystals (4.803 g), mp 184°-192° C. with rapid heating, are collected by filtration
  20. customMore crystals form in the filtrate and after 3 days
  21. customthese are collected
  22. customThe compound can be recrystallized from methanol-acetone in the freezer

Quellen und Nachweise

ORD-Eintrag
ord-00f7cddb015842f7a810c416a4b13e70
Quelldatensatz
uspto-grants-1993_12
Patentnummer
US05274089

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