5alpha-Dihydroprogesterone → Ganaxolone

HRID 1811506Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1811506
[CH3:1][Li].C[Mg]Cl.[CH3:6][C:7](=[O:28])[C@@H:8]1[C@:25]2([CH3:26])[C@H:11]([C@H:12]3[C@H:22]([CH2:23][CH2:24]2)[C@:20]2([CH3:21])[C@H:15]([CH2:16][C:17](=[O:27])[CH2:18][CH2:19]2)[CH2:14][CH2:13]3)[CH2:10][CH2:9]1>O1CCCC1.C(OCOCC)C>[CH3:6][C:7]([C@@H:8]1[C@@:25]2([CH3:26])[CH2:24][CH2:23][C@@H:22]3[C@@:20]4([CH3:21])[CH2:19][CH2:18][C@:17]([OH:27])([CH3:1])[CH2:16][C@@H:15]4[CH2:14][CH2:13][C@H:12]3[C@@H:11]2[CH2:10][CH2:9]1)=[O:28]

Komponenten

6

Edukt 3

HCID 928105alpha-DihydroprogesteroneHCID 178418332HCID 178418332, VerbindungHCID 178418348HCID 178418348, Verbindung

Produkt 1

HCID 6918305GanaxoloneAusbeute 94,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel2×HCID 10024DiethoxymethaneLösungsmittel

Reaktionsbedingungen

Temperatur
-50 °C

Versuchsvorschrift

A mixture of ferric chloride (anhydrous, 1.63 g, 10.06 mmol) in tetrahydrofuran (anhydrous, 35 ml) is cooled to −50° C. under nitrogen. Methyllithium (3M, 3.4 mL, 10.2 mmol) in diethoxymethane is added to the ferric chloride mixture, maintaining the temperature below −40° C. After this addition is complete methyl magnesium chloride solution (3M, 10.1 ml, 30.18 mmol) in tetrahydrofuran is added maintaining the internal temperature below −40° C. After 10 min. at −40° C., 5α-pregnane-3,20-dione (2.84 g, 9 mmol) is added in one portion with stirring. The temperature is brought to −20° C. and stirred for 3.5 hours. The reaction is quenched by addition of 3 ml of acetic acid and the tetrahydrofuran was removed in vacuo. The residue is partitioned between 100 ml of 3N HCl and 200 ml of ethyl acetate. The organic layer is washed with 1N sodium hydroxide and brine and the solvent is removed in vacuo to afford crude ganaxolone (94.8% purity by HPLC) (Table 1, entry 5)

Aufarbeitung

  1. temperaturemaintaining the temperature below −40° C
  2. additionAfter this addition
  3. additionis added
  4. temperaturemaintaining the internal temperature below −40° C
  5. customis brought to −20° C.
  6. stirringstirred for 3.5 hours
  7. customThe reaction is quenched by addition of 3 ml of acetic acid
  8. customthe tetrahydrofuran was removed in vacuo
  9. customThe residue is partitioned between 100 ml of 3N HCl and 200 ml of ethyl acetate
  10. washThe organic layer is washed with 1N sodium hydroxide and brine
  11. customthe solvent is removed in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-ecaf97ed9653492690bd1108104ddb01
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08362286B2

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