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

HRID 2350829Notes

Reaction equation

HRID 2350829 reaction equation
C[Li].[CH3:3][C@:4]12[CH2:21][CH2:20][C@H:19]3[C@@H:9]([CH2:10][CH2:11][C:12]4[C@:17]3([CH3:18])[CH:16]=[CH:15]C(=O)[CH:13]=4)[C@@H:8]1[CH2:7][CH2:6][C:5]2=[O:23].[C:24]([O:27][C:28](=[O:30])[CH3:29])(=O)[CH3:25].[Cl-].[NH4+]>ClC(Cl)C.O.[Cu]I>[C:28]([O:27][C:24]1[CH:13]=[C:12]2[C@:17]([CH3:18])([C@@H:16]([CH3:15])[CH:25]=1)[C@@H:19]1[C@H:9]([C@H:8]3[C@@:4]([CH2:21][CH2:20]1)([CH3:3])[C:5](=[O:23])[CH2:6][CH2:7]3)[CH2:10][CH2:11]2)(=[O:30])[CH3:29]

Participants

8

Reactant 4

HCID 7918Acetic AnhydrideHCID 13472Androsta-1,4-diene-3,17-dioneHCID 25517Ammonium ChlorideHCID 178418348HCID 178418348, compound

Product 1

HCID 108716113-Acetoxy-1alpha-methylandrosta-2,4-dien-17-oneYield 57.7%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 63651,1-DichloroethaneSolvent3×

Conditions

Temperature
-30 °C

Procedure

A suspension of 15.38 g of copper(I) iodide in 50 ml of dichloroethane is cooled to -30° C., combined at this temperature with 100 ml of methyllithium solution and stirred for one hour. A solution of 12.8 g of androsta-1,4-diene-3,17-dione [J. Am. Chem. Soc. 79:3920 (1957); Tetrahedron 4:201 (1958)] in 60 ml of dichloroethane is added dropwise to this mixture in such a way that the temperature does not rise beyond -10° C. After this addition is completed, the mixture is further stirred for 2 hours at 0° C. To this yellow-brownish solution, a solution of 8.62 g of acetic anhydride in 22 ml of dichloroethane is added and the mixture is stirred for one hour at room temperature. Then a solution of 8.3 g of ammonium chloride in 83 ml of water is added dropwise thereto. The organic phase is separated, the aqueous phase is extracted with methylene chloride and the combined organic phases washed with water. After drying over sodium sulfate, the mixture is concentrated under vacuum and the resultant crude product in recrystallized from hexane/acetone, thus obtaining 8.9 g of 3-acetoxy-1α-methylandrosta-2,4-dien-17-one, mp 104°-107° C.

Workup

  1. customdoes not rise beyond -10° C
  2. additionAfter this addition
  3. stirringthe mixture is further stirred for 2 hours at 0° C
  4. stirringthe mixture is stirred for one hour at room temperature
  5. customThe organic phase is separated
  6. extractionthe aqueous phase is extracted with methylene chloride
  7. washthe combined organic phases washed with water
  8. dry with materialAfter drying over sodium sulfate
  9. concentrationthe mixture is concentrated under vacuum
  10. customthe resultant crude product in recrystallized from hexane/acetone

Sources & evidence

ORD record
ord-7ac011ad6260426ab12cf2846f8b385e
Source dataset
uspto-grants-1989_10
Patent number
US04871482

Reaction notes

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