Hydrochloric Acid → HCID 15085897, compound

HRID 1089425Notes

Reaction equation

HRID 1089425 reaction equation
ICI.[F:4][C:5]1([F:35])[C@@H:22]([O:23]C2CCCCO2)[CH2:21][CH2:20][C@@:19]2([CH3:30])[C:6]1=[CH:7][CH2:8][C@@H:9]1[C@@H:18]2[CH2:17][CH2:16][C@@:14]2([CH3:15])[C@H:10]1[CH2:11][CH2:12][C@@H:13]2[O:31][CH:32]1[CH2:34][CH2:33]1.Cl>C(OCC)C.O1CCOCC1.[Zn]>[F:4][C:5]1([F:35])[C@@H:22]([OH:23])[CH2:21][CH2:20][C@@:19]2([CH3:30])[C:6]1=[CH:7][CH2:8][C@@H:9]1[C@@H:18]2[CH2:17][CH2:16][C@@:14]2([CH3:15])[C@H:10]1[CH2:11][CH2:12][C@@H:13]2[O:31][CH:32]1[CH2:33][CH2:34]1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 6346DiiodomethaneHCID 15085896HCID 15085896, compound

Product 1

HCID 15085897HCID 15085897, compound

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 3283Diethyl EtherSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a suspension of 0.3 g of zinc dust in 3 ml of diethyl ether is added 50 mg of cuprous chloride. The resulting mixture is refluxed for 30 minutes and then 1.06 g of diiodomethane is added. The resulting solution is refluxed for 30 minutes and 0.3 g of 4,4-difluoro-3β-(2-tetrahydropyranyloxy)-17β-ethenyloxyadrost-5-ene is added. The resulting mixture is refluxed for 16 hours and then diluted with 10 ml of diethyl ether and filtered. The solid which is separated is washed with ethyl acetate (3 times, 50 ml) and the combined filtrate and washings are washed with saturated aqueous ammonium chloride and dried over magnesium sulfate. The solvent is then removed under reduced pressure to leave a residual solid which is crude 4,4-difluoro-3β-(2-tetrahydropyranyloxy)-17β-(cyclopropyloxy)androst-5-ene containing some 17β-(cyclopropyloxy)cycloprop[5,6]androstane product. This material is treated with a catalytic amount of hydrochloric acid in aqueous dioxane to remove the tetrahydropyranyl protecting group. The solvent is then removed under reduced pressure to leave a residual crude solid which is purified by reverse phase high-pressure liquid chromatography to give 4,4-difluoro-17β-(cyclopropyloxy)androst-5-en-3β-ol. The compound has the following structural formula: ##STR4##

Workup

  1. temperatureThe resulting mixture is refluxed for 30 minutes
  2. temperatureThe resulting solution is refluxed for 30 minutes
  3. addition0.3 g of 4,4-difluoro-3β-(2-tetrahydropyranyloxy)-17β-ethenyloxyadrost-5-ene is added
  4. temperatureThe resulting mixture is refluxed for 16 hours
  5. filtrationfiltered
  6. customThe solid which is separated
  7. washis washed with ethyl acetate (3 times, 50 ml)
  8. washthe combined filtrate and washings are washed with saturated aqueous ammonium chloride
  9. dry with materialdried over magnesium sulfate
  10. customThe solvent is then removed under reduced pressure
  11. customto leave a residual solid which
  12. customto remove the tetrahydropyranyl protecting group
  13. customThe solvent is then removed under reduced pressure
  14. customto leave a residual crude solid which
  15. customis purified by reverse phase high-pressure liquid chromatography

Sources & evidence

ORD record
ord-024f3ca1c52d4b66bd6cf8b0b260087d
Source dataset
uspto-grants-1990_10
Patent number
US04966897

Reaction notes

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