1,4-Dioxane → HCID 22403821, compound

HRID 259820Notes

Reaction equation

HRID 259820 reaction equation
C[Sn](C)(C)[C:3]1[C:8]([F:9])=[CH:7][C:6]([N:10]2[CH2:14][CH:13]([CH2:15][NH:16][C:17](=[O:19])[CH3:18])[O:12][C:11]2=[O:20])=[CH:5][C:4]=1[F:21].[O:24]1[CH2:29][CH2:28][O:27][CH2:26]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>[CH3:26][O:27][C:28]1[C:29](=[O:24])[CH:5]=[CH:4][C:3]([C:3]2[C:8]([F:9])=[CH:7][C:6]([N:10]3[CH2:14][CH:13]([CH2:15][NH:16][C:17](=[O:19])[CH3:18])[O:12][C:11]3=[O:20])=[CH:5][C:4]=2[F:21])=[CH:8][CH:7]=1

Participants

4

Reactant 2

HCID 312751,4-DioxaneHCID 22403812HCID 22403812, compound

Product 1

HCID 22403821HCID 22403821, compoundYield 9%

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Conditions

Temperature
110 °C

Procedure

The (±)-N-[[3-[4-(trimethylstannyl)-3,5-difluorophenyl ]-2-oxo-5oxazolidinyl]methyl]acetamide (80 mg, 0.185 mmol) was dissolved in 1,4-dioxane (5 mL) and then treated with the 5-bromo-2-methoxytropolone (49.5 mg, .230 mmol). After degassing the solution 3 times with N2, the bis(triphenylphosphine)palladium(II) chloride (28 mg, .040 mmol) was added. The solution was degassed (3x) again, after which the reaction was heated to reflux (110° C.) for 5 h. At this point, the reaction was incomplete; more catalyst (28 mg, 0.040 mmol) was added and, after degassing (3×), the solution was again heated to reflux for 5 h. At this time, the reaction was still incomplete; the above process was repeated a third time with more fresh catalyst (28 mg). Finally, the solvent was removed in vacuo and the residual oil was dissolved in CH2Cl2 (50 mL). The CH2Cl2 solution was washed with aqueous KF (75 mL) and brine (50 mL). After drying over anhydrous Na2SO4, the organic layer was filtered and concentrated under reduced pressure to yield a foamy solid. This solid was purified first by preparative TLC (5% MeOH/CHCl3), and then by radial chromatography (eluting with a gradient of 0-5% MeOH in 10% CH3CN/CHCl3) to give 7 mg (9%) of the title compound as a solid with a HRMS (M+) calculated for C20H18F2N2O5 404.1184, found 404.1183.

Workup

  1. customAfter degassing the solution 3 times with N2
  2. customThe solution was degassed (3x) again
  3. temperatureafter which the reaction was heated
  4. customafter degassing (3×)
  5. temperaturethe solution was again heated
  6. temperatureto reflux for 5 h
  7. customFinally, the solvent was removed in vacuo
  8. dissolutionthe residual oil was dissolved in CH2Cl2 (50 mL)
  9. washThe CH2Cl2 solution was washed with aqueous KF (75 mL) and brine (50 mL)
  10. dry with materialAfter drying over anhydrous Na2SO4
  11. filtrationthe organic layer was filtered
  12. concentrationconcentrated under reduced pressure
  13. customto yield a foamy solid
  14. customThis solid was purified first by preparative TLC (5% MeOH/CHCl3)
  15. washby radial chromatography (eluting with a gradient of 0-5% MeOH in 10% CH3CN/CHCl3)

Sources & evidence

ORD record
ord-032a9935b3f1400699224bd5acacf7c2
Source dataset
uspto-grants-1996_06
Patent number
US05523403

Reaction notes

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