5alpha-Dihydroprogesterone → Ganaxolone

HRID 1811510Notes

Reaction equation

HRID 1811510 reaction equation
[CH3:1][Mg]Cl.[CH3:4][C:5](=[O:26])[C@@H:6]1[C@:23]2([CH3:24])[C@H:9]([C@H:10]3[C@H:20]([CH2:21][CH2:22]2)[C@:18]2([CH3:19])[C@H:13]([CH2:14][C:15](=[O:25])[CH2:16][CH2:17]2)[CH2:12][CH2:11]3)[CH2:8][CH2:7]1>C1COCC1>[CH3:4][C:5]([C@@H:6]1[C@@:23]2([CH3:24])[CH2:22][CH2:21][C@@H:20]3[C@@:18]4([CH3:19])[CH2:17][CH2:16][C@:15]([OH:25])([CH3:1])[CH2:14][C@@H:13]4[CH2:12][CH2:11][C@H:10]3[C@@H:9]2[CH2:8][CH2:7]1)=[O:26]

Participants

4

Reactant 2

HCID 928105alpha-DihydroprogesteroneHCID 178418332HCID 178418332, compound

Product 1

HCID 6918305Ganaxolone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-25 °C

Procedure

Ferrous chloride (4 g) is reacted with MeMgCl (3 equiv based on FeCl2) in THF (anhydrous, 200 mL) at −25° C. under nitrogen. To this mixture is then added 5α-Pregnane 3,20-dione (10 g). The mixture is stirred at −25° C. for 4 h and is quenched by adding acetic acid (32 mL). The mixture is concentrated in vacuo and the residue is stirred in 3N HCl (200 mL) for 6 h. The solid is collected by filtration, washed with water and dried. The crude product is dissolved in THF (33 mL) at reflux and filtered hot. The filtrate is mixed with water (45 mL) and the solid is collected by filtration, washed with water and dried. The solid is further slurried in ethyl acetate (50 mL) at 70° C. for 19 h. It is cooled to 5° C. and filtered, washed with cold ethyl acetate and dried to obtain ganaxolone.

Workup

  1. customis quenched
  2. additionby adding acetic acid (32 mL)
  3. concentrationThe mixture is concentrated in vacuo
  4. stirringthe residue is stirred in 3N HCl (200 mL) for 6 h
  5. filtrationThe solid is collected by filtration
  6. washwashed with water
  7. customdried
  8. dissolutionThe crude product is dissolved in THF (33 mL)
  9. temperatureat reflux
  10. filtrationfiltered hot
  11. additionThe filtrate is mixed with water (45 mL)
  12. filtrationthe solid is collected by filtration
  13. washwashed with water
  14. customdried
  15. waitThe solid is further slurried in ethyl acetate (50 mL) at 70° C. for 19 h
  16. temperatureIt is cooled to 5° C.
  17. filtrationfiltered
  18. washwashed with cold ethyl acetate
  19. customdried

Sources & evidence

ORD record
ord-dc38992da68945899655cd16c8c67955
Source dataset
uspto-grants-2013_01
Patent number
US08362286B2

Reaction notes

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