Pyridine, hydrofluoride (1:1) → HCID 69208006, compound

HRID 2222129Notes

Reaction equation

HRID 2222129 reaction equation
[CH3:1][O:2][C:3]1[C:4]([CH:22]=[CH2:23])=[CH:5][C:6]2[CH2:7][CH2:8][C@@H:9]3[C@@H:18]([C:19]=2[CH:20]=1)[CH2:17][CH2:16][C@@:14]1([CH3:15])[C@H:10]3[CH2:11][CH2:12][C@@H:13]1[OH:21].C([Sn-3](CCCC)(CCCC)C=C)CCC.[Cl-].[Li+].C1C=CN=CC=1.F>CN(C=O)C.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(C1C=C(C)C=C(C(C)(C)C)C=1O)(C)(C)C>[CH3:1][O:2][C:3]1[C:4]([CH:22]=[CH2:23])=[CH:5][C:6]2[CH2:7][CH2:8][C@@H:9]3[C@@H:18]([C:19]=2[CH:20]=1)[CH2:17][CH2:16][C@@:14]1([CH3:15])[C@H:10]3[CH2:11][CH2:12][C:13]1=[O:21]

Participants

9

Reactant 4

HCID 64774Pyridine, hydrofluoride (1:1)HCID 433294Lithium ChlorideHCID 46882739HCID 46882739, compoundHCID 178477757HCID 178477757, compound

Product 1

HCID 69208006HCID 69208006, compoundYield 60%

Reagents, catalysts & solvents 4

HCID 314042,6-Di-tert-butyl-4-methylphenolCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

Alternate synthesis of 2-methoxy-3-(vinyl)estra-1,3,5(10)-triene-17β-ol (Compound #25a): Into a solution of 3-triflate-2-methoxyestra-1,3,5(10)-trien-17β-ol (218 mg, 0.5 mmol, prepared as in Shi J. Am. Chem. Soc. 2002, 124, 6921) in 4 mL DMF (anhydrous), was added tributyl(vinyl)Tin(1) (200 μL, 0.6 mmol), lithium chloride (85 mg, 2 mmol), dichlorobis(triphenylphosphine)palladium (II) (10 mg, 0.05 mmol), 2,6-di-tert-butyl-4-methylphenol (2 mg) at room temperature. The reaction was heated at 90° C. for 24 h and then cooled to room temperature. After adding HF-pyridine (4 mL) the reaction mixture was stirred for 16 h. After diluting with EtOAc (20 mL) the reaction mixture was filtered through Celite filter agent and the combined organics were washed with 1 N HCl (1×100 mL), water (1×100 mL), and brine (1×100 mL), then dried with sodium sulfate, filtered, and concentrated via rotary evaporation to give a semi solid viscous oil. The product was purified on a flash silica gel column eluted with a hexane/EtOAc 2:1 mixture to give a white solid product (140 mg, 60%). 1H NMR (CDCl3 δ 7.20 (s, 1 H), 7.00 (dd, J=14, 11 Hz, vinyl, 1H) 6.80 (s, 1 H), 5.70 (d, J=18 Hz, vinyl, 1H), 5.22 (d, J=11 Hz, vinyl, 1H), 3.85 (s, 3H), 2.72 (t, J=4 Hz, 1H), 2.85 (dd, J=5 Hz, 2H), 2.44-1.88 (m, 6 H), 1.80-1.15 (m, 8H), 0.80 (s, 3 H).

Workup

  1. temperaturecooled to room temperature
  2. filtrationwas filtered through Celite
  3. filtrationfilter agent
  4. washthe combined organics were washed with 1 N HCl (1×100 mL), water (1×100 mL), and brine (1×100 mL)
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated via rotary evaporation
  8. customto give a semi solid viscous oil
  9. customThe product was purified on a flash silica gel column
  10. washeluted with a hexane/EtOAc 2:1 mixture

Sources & evidence

ORD record
ord-b20f5c5abc4b4cb89ddfe6cb63e747b1
Source dataset
uspto-grants-2008_05
Patent number
US07371741B2

Reaction notes

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