Methyl iodide → 16alpha-Fluoro-1beta,6beta-dimethyl-7-methylenandrost-4-ene-3,17-dione

HRID 621621Notes

Reaction equation

HRID 621621 reaction equation
C1CO[CH:20]2[CH:3]([CH2:4][C:5]34O[C@H:6]3[C:7](=[CH2:30])[C@@H:8]3[C@@H:17]([C@@:18]4([CH3:24])[C@@H:19]2[CH3:23])[CH2:16][CH2:15][C@@:13]2([CH3:14])[C@H:9]3[CH2:10][C@:11]3([F:29])OCC[O:25][CH:12]32)[O:2]1.[Mg].[CH3:33]I>C1C=CC=CC=1.C(OCC)C>[F:29][C@@H:11]1[CH2:10][C@H:9]2[C@H:8]3[C@H:17]([CH2:16][CH2:15][C@:13]2([CH3:14])[C:12]1=[O:25])[C@:18]1([CH3:24])[C:5](=[CH:4][C:3](=[O:2])[CH2:20][C@H:19]1[CH3:23])[C@H:6]([CH3:33])[C:7]3=[CH2:30]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 5462224MagnesiumHCID 867429553,17-Bis(ethylenedioxy)-5,6alpha-epoxy-16alpha-fluoro-1beta-methyl-7-methylenandrostane

Product 1

HCID 1863203316alpha-Fluoro-1beta,6beta-dimethyl-7-methylenandrost-4-ene-3,17-dioneYield 80.5%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 3283Diethyl EtherSolvent

Procedure

3,17-bis(ethylenedioxy)-5,6α-epoxy-16α-fluoro-1β-methyl-7-methylenandrostane (431 mg) in benzene solution (40 ml), is added to a Grignard mixture prepared from magnesium (122 mg) and methyl iodide (710 mg) in diethylether (10 ml). Solvent is removed until the boiling point reaches ~78° C. Heating is then continued for a further 3 hrs. Ice and saturated ammonium chloride solution are added, the product extracted with ethyl acetate and the organic layer is evaporated in vacuo after having washed and dried it. The residue is dissolved in a 2:1 mixture of acetic acid and water (10 ml) and the solution heated for about 6 hrs at 40°-50° C. Then water is added and the product extracted with ethyl acetate. The organic layer is washed with sodium bicarbonate solution, dried and evaporated in vacuo. The residue is submitted to column chromatography thus giving pure 16α-fluoro-1β,6β-dimethyl-7-methylenandrost-4-ene-3,17-dione (275 mg).

Workup

  1. customSolvent is removed until the boiling point
  2. customreaches ~78° C
  3. temperatureHeating
  4. additionIce and saturated ammonium chloride solution are added
  5. extractionthe product extracted with ethyl acetate
  6. customthe organic layer is evaporated in vacuo
  7. washafter having washed
  8. customdried it
  9. dissolutionThe residue is dissolved in a 2:1 mixture of acetic acid and water (10 ml)
  10. temperaturethe solution heated for about 6 hrs at 40°-50° C
  11. additionThen water is added
  12. extractionthe product extracted with ethyl acetate
  13. washThe organic layer is washed with sodium bicarbonate solution
  14. customdried
  15. customevaporated in vacuo

Sources & evidence

ORD record
ord-b6736ce1a3d04ad681e652de49cdcafb
Source dataset
uspto-grants-1989_04
Patent number
US04824830

Reaction notes

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