Androstenedione → 6-Methylideneandrost-4-ene-3,17-dione

HRID 2210069Notes

Reaction equation

HRID 2210069 reaction equation
[C:1]([O-])(=O)C.[Na+].C(OCOCC)C.P(Cl)(Cl)(Cl)=O.[CH3:18][C@:19]12[CH2:36][CH2:35][C@H:34]3[C@@H:24]([CH2:25][CH2:26][C:27]4[C@:32]3([CH3:33])[CH2:31][CH2:30][C:29](=[O:37])[CH:28]=4)[C@@H:23]1[CH2:22][CH2:21][C:20]2=[O:38].C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)(Cl)Cl>[CH2:1]=[C:26]1[C:27]2[C@:32]([CH3:33])([CH2:31][CH2:30][C:29](=[O:37])[CH:28]=2)[C@@H:34]2[C@H:24]([C@H:23]3[C@@:19]([CH2:36][CH2:35]2)([CH3:18])[C:20](=[O:38])[CH2:21][CH2:22]3)[CH2:25]1

Participants

7

Reactant 5

HCID 6128AndrostenedioneHCID 10024DiethoxymethaneHCID 10340Sodium CarbonateHCID 24813Phosphorus oxychlorideHCID 517045Sodium Acetate

Product 1

HCID 129518006-Methylideneandrost-4-ene-3,17-dioneYield 60%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A mixture of sodium acetate (1 g), anhydrous chloroform (30 ml), formaldehyde diethyl acetal (30 ml, 0.24 mol), phosphoryl chloride (3.8 ml, 0.04 mol), and androst-4-ene-3,17-dione (0.78 g, 2.7 mmol) was stirred at reflux for about 7 hours, i.e. until the starting material had disappeared. The suspension was allowed to cool and under vigorous stirring a saturated sodium carbonate solution was added dropwise until the pH of the aqueous layer became alkaline. The organic layer was separated, neutralized with water washings, and dried with sodium sulfate. After concentration under reduced pressure the oily residue was purified by chromatography on silica gel using hexane/ethylacetate as eluant. Thus almost pure 6-methylenandrost-4-ene-3,17-dione was obtained in 60% yield (0.843 g).

Workup

  1. temperatureat reflux for about 7 hours
  2. temperatureto cool
  3. additionwas added dropwise until the pH of the aqueous layer
  4. customThe organic layer was separated
  5. dry with materialdried with sodium sulfate
  6. concentrationAfter concentration under reduced pressure the oily residue
  7. customwas purified by chromatography on silica gel

Sources & evidence

ORD record
ord-2e926a70409845098e8c937d925ae080
Source dataset
uspto-grants-1995_10
Patent number
US05457097

Reaction notes

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