Toluene → HCID 67104753, compound

HRID 860860Notes

Reaction equation

HRID 860860 reaction equation
[Br:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:12][CH2:13][CH2:14]Br)[CH:8]=2)[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[C:22]1([CH3:28])C=C[CH:25]=[CH:24][CH:23]=1.C[N:30](C=O)C>>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([O:12][CH2:13][CH2:14][N:30]1[CH2:25][CH2:24][CH2:23][C@H:22]1[CH3:28])[CH:6]=[CH:5]2

Participants

5

Reactant 4

HCID 1140TolueneHCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 22131449HCID 22131449, compound

Product 1

HCID 67104753HCID 67104753, compound

Conditions

Temperature
50 °C

Procedure

The product from Example 37A (495 mg, 1.5 mmol), potassium carbonate (207 mg, 1.5 mmol), and the above toluene solution were suspended into DMF (3 mL) and heated at 50° C. overnight. The reaction mixture was brought to room temperature and partitioned between 0.2 M aqueous NaOH (20 mL) and dichloromethane (10 mL). The aqueous phase was separated and extracted with dichloromethane, and the combined organic phases were washed with 0.2 M aqueous NaOH, dried (Na2SO4), and filtered quickly through a silica plug with a 0 to 10% methanol/dichloromethane gradient. The filtrate was partitioned between water and 2:1 dichloromethane/hexanes. The aqueous phase was separated and extracted with 20% hexanes/dichloromethane, and the combined organic phases were concentrated and chromatographed through silica with a little hexanes/dichloromethane followed by a gradient of 0 to 10% methanol/dichloromethane. The appropriate fractions were combined and concentrated under high vacuum to provide 451 mg of a 6:1 mixture of title compound and starting dibromide which was used in the next step without further purification; MS (ESI APCI) m/z 334/336 (M+H)+.

Workup

  1. customwas brought to room temperature
  2. custompartitioned between 0.2 M aqueous NaOH (20 mL) and dichloromethane (10 mL)
  3. customThe aqueous phase was separated
  4. extractionextracted with dichloromethane
  5. washthe combined organic phases were washed with 0.2 M aqueous NaOH
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered quickly through a silica plug with a 0 to 10% methanol/dichloromethane gradient
  8. customThe filtrate was partitioned between water and 2:1 dichloromethane/hexanes
  9. customThe aqueous phase was separated
  10. extractionextracted with 20% hexanes/dichloromethane
  11. concentrationthe combined organic phases were concentrated
  12. customchromatographed through silica with a little hexanes/dichloromethane
  13. concentrationconcentrated under high vacuum
  14. customto provide

Sources & evidence

ORD record
ord-6097037a83d34dc4a997a31136aa9439
Source dataset
uspto-grants-2006_12
Patent number
US07153889B2

Reaction notes

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