Acetic Acid → 4-Methyl-4-aza-androst-5-ene-3,17-dione

HRID 840182

Reaction equation

HRID 840182 reaction equation
[CH3:1][C@:2]12[CH2:19][CH2:18][C@H:17]3[C@@H:7]([CH2:8][CH2:9][C:10]4[C@:15]3([CH3:16])[CH2:14][CH2:13][C:12](=[O:20])C=4)[C@@H:6]1[CH2:5][CH2:4][C:3]2=[O:21].[Cl-].[CH3:23][NH3+:24].C(O)(=O)C>C(OCC)(=O)C>[CH3:23][N:24]1[C:12](=[O:20])[CH2:13][CH2:14][C@@:15]2([CH3:16])[C:10]1=[CH:9][CH2:8][C@@H:7]1[C@@H:17]2[CH2:18][CH2:19][C@@:2]2([CH3:1])[C@H:6]1[CH2:5][CH2:4][C:3]2=[O:21]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 6128AndrostenedioneHCID 11637Methanamine, hydrochloride (1:1)

Product 1

HCID 100634474-Methyl-4-aza-androst-5-ene-3,17-dione

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Androst-4-ene-3,17-dione is oxidized into 5-oxo-4-nor-3,5-seco-androstane-5,17-dione as in Example 16A (seco-acid). The seco-acid (9.000 g, 31.423 mmol) is slurried with methylammonium chloride (19.5000 g, 288.80 mmol) into acetic acid (75 mL) and heated to reflux under an inert atmosphere. After 3 days, the reaction mixture is allowed to cool to room temperature and diluted with ethyl acetate (EtOAc, 500 mL). The organic solution is washed with water (3×200 mL), saturated aqueous NaHCO3 (2×200 mL) and brine (200 mL), then dried over magnesium sulfate (MgSO4), filtered, concentrated and purified by flash chromatography (1:1:2 EtOAc/CH2Cl2) to afford 4-methyl-4-aza-androst-5-ene-3,17-dione (aza-dione).

Workup

  1. temperatureheated
  2. temperatureto reflux under an inert atmosphere
  3. washThe organic solution is washed with water (3×200 mL), saturated aqueous NaHCO3 (2×200 mL) and brine (200 mL)
  4. dry with materialdried over magnesium sulfate (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by flash chromatography (1:1:2 EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-5646ca0d3e0443e79f977e76764b1bf1
Source dataset
uspto-grants-2002_04
Patent number
US06365597B1

Linked notes

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