1,4-Dioxane → HCID 22403821, compound

HRID 259821Notes

Reaction equation

HRID 259821 reaction equation
I[C:2]1[C:7]([F:8])=[CH:6][C:5]([N:9]2[CH2:13][CH:12]([CH2:14][NH:15][C:16](=[O:18])[CH3:17])[O:11][C:10]2=[O:19])=[CH:4][C:3]=1[F:20].[O:21]1[CH2:26][CH2:25][O:24][CH2:23]C1>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>[CH3:23][O:24][C:25]1[C:26](=[O:21])[CH:4]=[CH:3][C:2]([C:2]2[C:7]([F:8])=[CH:6][C:5]([N:9]3[CH2:13][CH:12]([CH2:14][NH:15][C:16](=[O:18])[CH3:17])[O:11][C:10]3=[O:19])=[CH:4][C:3]=2[F:20])=[CH:7][CH:6]=1

Participants

4

Reactant 2

HCID 312751,4-DioxaneHCID 21981983HCID 21981983, compound

Product 1

HCID 22403821HCID 22403821, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Conditions

Temperature
110 °C

Procedure

The (±)-N-[[3-(4-iodo-3,5-difluorophenyl)-2-oxo-5-oxazolidinyl]methyl ]acetamide (250 mg, 0.631 mmol) was dissolved in 1,4-dioxane (15 mL) and then treated with the stannyltropone (226 mg, 0.757 mmol). After degassing the solution 3 times with N2, the bis(triphenylphosphine)palladium(II) chloride (70 mg, 0.10 mmol) was added. The solution was degassed again (3×) and then it was heated to reflux (110° C.) for 7 h. At this point, the reaction was incomplete; fresh catalyst (70 mg, 0.10 mmol) was added, and after degassing again (3×), the solution was again heated to reflux for 7 h. At this time, the solvent was removed in vacuo and the residual oil was dissolved in CH2Cl2 (50 mL). The CH2Cl2 solution was washed with aqueous KF (40 mL) and brine (40 mL). After drying over anhydrous Na2SO4, the organic layer was filtered and concentrated under reduced pressure to yield a foamy, brown solid. This solid was chromatographed on silica gel (100 g), eluting with a gradient of 0-10% MeOH in 10% CH3CN/CHCl3 to give impure product. This product was repurified by preparative TLC (5% MeOH/CHCl3) to yield 72 mg (28%) of the title compound as an off-white solid with mp 218° C. (dec) and identical in all respects to material prepared as described above.

Workup

  1. additiontreated with the stannyltropone (226 mg, 0.757 mmol)
  2. customAfter degassing the solution 3 times with N2
  3. customThe solution was degassed again (3×)
  4. temperatureit was heated
  5. customafter degassing again (3×)
  6. temperaturethe solution was again heated
  7. temperatureto reflux for 7 h
  8. customAt this time, the solvent was removed in vacuo
  9. dissolutionthe residual oil was dissolved in CH2Cl2 (50 mL)
  10. washThe CH2Cl2 solution was washed with aqueous KF (40 mL) and brine (40 mL)
  11. dry with materialAfter drying over anhydrous Na2SO4
  12. filtrationthe organic layer was filtered
  13. concentrationconcentrated under reduced pressure
  14. customto yield a foamy, brown solid
  15. customThis solid was chromatographed on silica gel (100 g)
  16. washeluting with a gradient of 0-10% MeOH in 10% CH3CN/CHCl3
  17. customto give impure product
  18. customThis product was repurified by preparative TLC (5% MeOH/CHCl3)

Sources & evidence

ORD record
ord-51de9e9344ae459c89deabf8d8aad90f
Source dataset
uspto-grants-1996_06
Patent number
US05523403

Reaction notes

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