Water → 4-Androstene-3,17-dione, 1alpha-methyl-

HRID 1415846Notes

Reaction equation

HRID 1415846 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:12](=[O:20])[CH:11]=4)[C@@H:6]1[CH2:5][CH2:4][C:3]2=[O:21].[CH3:22][Al](C)C.O>O1CCOCC1.C1(C)C=CC=CC=1.[Cu]Br>[CH3:22][C@@H:14]1[C@@:15]2([CH3:16])[C:10]([CH2:9][CH2:8][C@@H:7]3[C@@H:17]2[CH2:18][CH2:19][C@@:2]2([CH3:1])[C@H:6]3[CH2:5][CH2:4][C:3]2=[O:21])=[CH:11][C:12](=[O:20])[CH2:13]1

Participants

7

Reactant 3

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

Product 1

HCID 109575614-Androstene-3,17-dione, 1alpha-methyl-

Reagents, catalysts & solvents 3

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

Conditions

Temperature
25 °C

Procedure

2.84 g (10 mmol) of androsta-1,4-diene-3,17-dione is dissolved in 20 ml of anhydrous dioxane under nitrogen atmosphere. 143.3 mg (1 mmol) of copper(I) bromide is added and the solution is heated to 25° C. Then 9.4 ml (11 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. For hydrolysis, 0.54 ml of water mixed with 5 ml of dioxane is carefully added to the reaction and the solution is stirred for 15 minutes more. The inorganic solid is suctioned off and washed again with 30 ml of dioxane. After concentration by evaporation of the solution, 3.1 g of 1α-methylandrost-4-ene-3,17-dione is obtained, that is dissolved in 8 ml of methanol and cooled to -5° C. internal. temperature. 0.18 g of sodium borohydride is added to 0.5 ml of water cooled to 5° C. and the sodium borohydride-water solution is added to the solution of 1α-methyl-androst-4-ene-3,17-dione so that the temperature does not rise above -5° C. Then it is stirred for 40 minutes more at -5° C. After DC check to determine whether the reaction has occurred, 0.33 ml of acetic acid in 1 ml of water is carefully added until no more gas generation is detectable. The solution is taken up in 50 ml of ethyl acetate and washed twice with 20 ml of water each. The organic phase is dried with sodium sulfate. After concentration by evaporation of the solution and recrystallization from acetone, 2.29 g of 17β-hydroxy-1α-methyl-androst-4-en-3-one (75% of theory) of a melting point of 195° C. is obtained.

Workup

  1. customdoes not rise above 35° C
  2. additionis carefully added to the reaction
  3. stirringthe solution is stirred for 15 minutes more
  4. washwashed again with 30 ml of dioxane
  5. concentrationAfter concentration
  6. customby evaporation of the solution

Sources & evidence

ORD record
ord-92e66f645b07473a94056f9d1024ca8b
Source dataset
uspto-grants-1999_06
Patent number
US05908944

Reaction notes

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