5alpha-Dihydroprogesterone → Ganaxolone

HRID 1811508Notes

Reaction equation

HRID 1811508 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>O1CCOCC1>[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 312751,4-DioxaneSolvent

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 dioxane (anhydrous, 200 mL) at −25° C. for 5 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. The ethyl acetate slurry step is repeated one more time to obtain purified ganaxolone.

Workup

  1. customobtained
  2. customat −25° C.
  3. customfor 5 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

Sources & evidence

ORD record
ord-33b3ecba88b04c0d995a957554aad255
Source dataset
uspto-grants-2013_01
Patent number
US08362286B2

Reaction notes

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