Water → 3-Acetoxy-1alpha-methylandrosta-2,4-dien-17-one

HRID 1415849Notes

Reaction equation

HRID 1415849 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])[CH:14]=[CH:13]C(=O)[CH:11]=4)[C@@H:6]1[CH2:5][CH2:4][C:3]2=[O:21].C[Al](C)C.[C:26]([O:29][C:30](=[O:32])[CH3:31])(=O)[CH3:27].O>O1CCOCC1.C1(C)C=CC=CC=1.[Cu]Br>[C:30]([O:29][C:26]1[CH:11]=[C:10]2[C@:15]([CH3:16])([C@@H:14]([CH3:13])[CH:27]=1)[C@@H:17]1[C@H:7]([C@H:6]3[C@@:2]([CH2:19][CH2:18]1)([CH3:1])[C:3](=[O:21])[CH2:4][CH2:5]3)[CH2:8][CH2:9]2)(=[O:32])[CH3:31]

Participants

8

Reactant 4

HCID 962WaterHCID 7918Acetic AnhydrideHCID 13472Androsta-1,4-diene-3,17-dioneHCID 16682925Trimethylaluminum

Product 1

HCID 108716113-Acetoxy-1alpha-methylandrosta-2,4-dien-17-oneYield 70%

Reagents, catalysts & solvents 3

HCID 24593copper(I) bromideCatalystHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
25 °C

Procedure

14.2 g (50 mmol) of androsta-1,4-diene-3,17-dione is dissolved in 100 ml of anhydrous dioxane under nitrogen atmosphere. 716 mg (5 mmol) of copper(I) bromide is added and the solution is heated to 25° C. Then 47 ml (55 mmol) of a 10% solution of trimethyl aluminum in toluene is added to the reaction so that the temperature does not rise above 35° C. Then it is stirred for 1.5 hours more at 35° C. 16.84 g (0.165 mol) of acetic anhydride is added at 35° C. and the reaction solution is stirred for 1 hour more at 30° C. For completion of the reaction it is then heated for 15 minutes to 60° C. After cooling of the solution to 20° C., 4 ml of water dissolved in 20 ml of dioxane is added to the reaction for the hydrolysis and the solution is stirred again for 15 minutes. The inorganic solid is suctioned off on diatomaceous earth and the solid is washed again with 50 ml of dioxane. After concentration by evaporation of the solution on a rotary evaporator, 18 g of crude product is obtained, that is chromatographed on silica gel with hexane and an increasing part of ethyl acetate as eluent. After concentration by evaporation of the fractions, 11.4 g of 3-acetoxy-1α-methyl-androsta-2,4-dien-17-one (70% of theory) is obtained as viscous material that can be recrystallized from diisopropylether.

Workup

  1. customdoes not rise above 35° C
  2. stirringthe reaction solution is stirred for 1 hour more at 30° C
  3. customFor completion of the reaction it
  4. temperatureis then heated for 15 minutes to 60° C
  5. temperatureAfter cooling of the solution to 20° C.
  6. additionis added to the reaction for the hydrolysis
  7. stirringthe solution is stirred again for 15 minutes
  8. washthe solid is washed again with 50 ml of dioxane
  9. concentrationAfter concentration
  10. customby evaporation of the solution
  11. customon a rotary evaporator
  12. custom18 g of crude product is obtained
  13. customthat is chromatographed on silica gel with hexane
  14. concentrationAfter concentration
  15. customby evaporation of the fractions

Sources & evidence

ORD record
ord-28a6e8d558fa4cbcb06e93cd2a835986
Source dataset
uspto-grants-1999_06
Patent number
US05908944

Reaction notes

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