Ethylene Glycol → 17beta-{N-[1-(4-Methoxyphenyl)-1-methylethyl]carbamoyl}androsta-3,5-diene-3-carboxylic acid

HRID 1735526Notes

Reaction equation

HRID 1735526 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([NH:12][C:13]([C@H:15]2[CH2:20][CH2:19][C@H:18]3[C@H:21]4[C@H:31]([CH2:32][CH2:33][C@:16]23[CH3:17])[C@:29]2([CH3:30])[C:24]([CH:25]=C(C#N)[CH2:27][CH2:28]2)=[CH:23][CH2:22]4)=[O:14])([CH3:11])[CH3:10])=[CH:5][CH:4]=1.[OH-:36].[K+].Cl.[CH2:39]([OH:42])[CH2:40]O>O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([NH:12][C:13]([C@H:15]2[CH2:20][CH2:19][C@H:18]3[C@H:21]4[C@H:31]([CH2:32][CH2:33][C@:16]23[CH3:17])[C@:29]2([CH3:30])[C:24]([CH:25]=[C:40]([C:39]([OH:42])=[O:36])[CH2:27][CH2:28]2)=[CH:23][CH2:22]4)=[O:14])([CH3:11])[CH3:10])=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 174Ethylene GlycolHCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 15380263N-[1-(4-methoxyphenyl)-1-methylethyl]-3-cyanoandrosta-3,5-diene-17beta-carboxamide

Product 1

HCID 1538026417beta-{N-[1-(4-Methoxyphenyl)-1-methylethyl]carbamoyl}androsta-3,5-diene-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

280 mg of N-[1-(4-methoxyphenyl)-1-methylethyl]-3-cyanoandrosta-3,5-diene-17β-carboxamide [prepared as described in step (c) above] were suspended in 15 ml of ethylene glycol, and a solution of 2.2 g of potassium hydroxide in 5 ml of water was added to the resulting suspension. The mixture was then heated under reflux for 24 hours in a nitrogen stream. At the end of this time, the reaction mixture was cooled to room temperature and made acidic by the addition of 10% w/v aqueous hydrochloric acid, and then the mixture was extracted with methylene chloride. The extract was washed with water and with a saturated aqueous solution of sodium chloride, in that order, after which it was dried over anhydrous sodium sulfate. The solvent was then removed from the mixture by evaporation under reduced pressure. The residue was recrystallized from a mixture of acetone and diethyl ether, and the resulting crystals were collected by filtration. The mother liquor was purified by silica gel column chromatography using a gradient elution method, with mixtures of methylene chloride and acetone in ratios ranging from 9:1 to 7:3 by volume as the eluent, to give 268 mg of the title compound as white powdery crystals.

Workup

  1. temperatureThe mixture was then heated
  2. temperatureunder reflux for 24 hours in a nitrogen stream
  3. additionmade acidic by the addition of 10%
  4. extractionthe mixture was extracted with methylene chloride
  5. washThe extract was washed with water and with a saturated aqueous solution of sodium chloride, in that order
  6. dry with materialafter which it was dried over anhydrous sodium sulfate
  7. customThe solvent was then removed from the mixture by evaporation under reduced pressure
  8. customThe residue was recrystallized from a mixture of acetone and diethyl ether
  9. filtrationthe resulting crystals were collected by filtration
  10. customThe mother liquor was purified by silica gel column chromatography
  11. washa gradient elution method

Sources & evidence

ORD record
ord-5880c74f835549ad83723af687c99c3d
Source dataset
uspto-grants-1996_07
Patent number
US05536714

Reaction notes

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