5alpha-Dihydroprogesterone → Ganaxolone

HRID 1811505Notes

Reaction equation

HRID 1811505 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>O1CCCC1>[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 8028TetrahydrofuranSolvent2×

Procedure

A solution of ferric chloride (anhydrous, 2.14 g, 13.2 mmol) in tetrahydrofuran (anhydrous, 40 mL) is cooled to −50° C. Methyl magnesium chloride (3M, 17.6 ml, 52.8 mmol) in tetrahydrofuran is added to this mixture dropwise maintaining the internal temperature below −40° C. After 10 min at −40° C., 5α-pregnane-3,20-dione (3.48 g, 11 mmol) is added in one portion with stirring. The temperature is brought to −20° C. over 30 min. and stirred 2 hours. The reaction mixture is quenched with 100 ml of 2N HCl and the product extracted with 100 ml ethyl acetate. The organic layer is washed with 2N NaOH and brine and the solvent removed in vacuo to afford crude ganaxolone (80.2% purity by HPLC (Table 1, entry 4).

Workup

  1. temperaturedropwise maintaining the internal temperature below −40° C
  2. waitThe temperature is brought to −20° C. over 30 min.
  3. stirringstirred 2 hours
  4. customThe reaction mixture is quenched with 100 ml of 2N HCl
  5. extractionthe product extracted with 100 ml ethyl acetate
  6. washThe organic layer is washed with 2N NaOH and brine
  7. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-c4a32d7e5a734e26b116c7f70801ee9a
Source dataset
uspto-grants-2013_01
Patent number
US08362286B2

Reaction notes

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