5alpha-Dihydroprogesterone → Ganaxolone

HRID 1811511Notes

Reaction equation

HRID 1811511 reaction equation
[Li][CH3:2].[CH3:3][C:4](=[O:25])[C@@H:5]1[C@:22]2([CH3:23])[C@H:8]([C@H:9]3[C@H:19]([CH2:20][CH2:21]2)[C@:17]2([CH3:18])[C@H:12]([CH2:13][C:14](=[O:24])[CH2:15][CH2:16]2)[CH2:11][CH2:10]3)[CH2:7][CH2:6]1>C1(C)C=CC=CC=1>[CH3:3][C:4]([C@@H:5]1[C@@:22]2([CH3:23])[CH2:21][CH2:20][C@@H:19]3[C@@:17]4([CH3:18])[CH2:16][CH2:15][C@:14]([OH:24])([CH3:2])[CH2:13][C@@H:12]4[CH2:11][CH2:10][C@H:9]3[C@@H:8]2[CH2:7][CH2:6]1)=[O:25]

Participants

4

Reactant 2

HCID 928105alpha-DihydroprogesteroneHCID 178418348HCID 178418348, compound

Product 1

HCID 6918305Ganaxolone

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
-25 °C

Procedure

Ferrous chloride (4 g) is reacted with MeLi (3 equiv. based on FeCl2) in toluene (anhydrous, 200 mL) at −25° C. under nitrogen. 5α-pregnane 3,20-dione (10 g) is then added to this mixture. The mixture is stirred at −25° C. for 5 h. It 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 8 h. It is cooled to 5° C. and filtered, washed with cold ethyl acetate and dried to obtain ganaxolone.

Workup

  1. customIt is 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 8 h
  16. temperatureIt is cooled to 5° C.
  17. filtrationfiltered
  18. washwashed with cold ethyl acetate
  19. customdried

Sources & evidence

ORD record
ord-9340d10cc5cc4e2cbefd5fddedb1aad9
Source dataset
uspto-grants-2013_01
Patent number
US08362286B2

Reaction notes

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