5alpha-Dihydroprogesterone → Ganaxolone

HRID 1811507Notes

Reaction equation

HRID 1811507 reaction equation
[CH3:1][C:2](=[O:23])[C@@H:3]1[C@:20]2([CH3:21])[C@H:6]([C@H:7]3[C@H:17]([CH2:18][CH2:19]2)[C@:15]2([CH3:16])[C@H:10]([CH2:11][C:12](=[O:22])[CH2:13][CH2:14]2)[CH2:9][CH2:8]3)[CH2:5][CH2:4]1.[CH3:24][Mg]Cl>O1CCCC1>[CH3:1][C:2]([C@@H:3]1[C@@:20]2([CH3:21])[CH2:19][CH2:18][C@@H:17]3[C@@:15]4([CH3:16])[CH2:14][CH2:13][C@:12]([OH:22])([CH3:24])[CH2:11][C@@H:10]4[CH2:9][CH2:8][C@H:7]3[C@@H:6]2[CH2:5][CH2:4]1)=[O:23]

Participants

4

Reactant 2

HCID 928105alpha-DihydroprogesteroneHCID 178418332HCID 178418332, compound

Product 1

HCID 6918305Ganaxolone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

5α-Pregnane 3,20-dione (10 g) is reacted with a reagent obtained by reacting FeCl3 (5.2 g) and MeMgCl (4 equiv, based on FeCl3) in anhydrous tetrahydrofuran (200 mL) at −25° C. for 3 h. The reaction is quenched with acetic acid (32 ml). The reaction mixture is concentrated in vacuo and the residue is stirred with 3N HCl for 6 h. The solid is collected by filtration, washed with water and dried at 50° C. under vacuum to obtain crude ganaxolone. The crude product is dissolved in THF (33 mL) at reflux and filtered hot. The filtrate is added with water (45 mL) to obtain a suspension, which is collected by filtration, washed with water and dried. The dried product is further slurried in ethyl acetate (50 mL) at 70° C. for 19 h. The suspension is cooled to 0° C. and filtered, washed with cold ethyl acetate and dried to obtain ganaxolone.

Workup

  1. customobtained
  2. customat −25° C.
  3. customfor 3 h
  4. customThe reaction is quenched with acetic acid (32 ml)
  5. concentrationThe reaction mixture is concentrated in vacuo
  6. filtrationThe solid is collected by filtration
  7. washwashed with water
  8. customdried at 50° C. under vacuum
  9. customto obtain crude ganaxolone
  10. temperatureat reflux
  11. filtrationfiltered hot
  12. additionThe filtrate is added with water (45 mL)
  13. customto obtain a suspension, which
  14. filtrationis collected by filtration
  15. washwashed with water
  16. customdried
  17. waitThe dried product is further slurried in ethyl acetate (50 mL) at 70° C. for 19 h
  18. filtrationfiltered
  19. washwashed with cold ethyl acetate
  20. customdried

Sources & evidence

ORD record
ord-d451dc4ec800465aa96da0ecb05be108
Source dataset
uspto-grants-2013_01
Patent number
US08362286B2

Reaction notes

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