Potassium Carbonate → HCID 59472584, compound

HRID 885145Notes

Reaction equation

HRID 885145 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1F)[CH:5]=O.[CH3:11][C:12]1[N:13]=[CH:14][NH:15][CH:16]=1.[C:17]([O-])([O-])=O.[K+].[K+].[N+](=C(P(=O)(OC)OC)C(=O)C)=[N-]>CN(C=O)C.CO.O.CCO>[C:5]([C:4]1[CH:7]=[CH:8][C:9]([N:15]2[CH:16]=[C:12]([CH3:11])[N:13]=[CH:14]2)=[C:2]([F:1])[CH:3]=1)#[CH:17]

Participants

9

Reactant 4

HCID 11430Potassium Carbonate2×HCID 5880883,4-DifluorobenzaldehydeHCID 136023029(1E)-1-diazo-1-dimethoxyphosphorylpropan-2-oneHCID 178418800HCID 178418800, compound

Product 1

HCID 59472584HCID 59472584, compound

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 887MethanolSolvent2×HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

3,4-Difluorobenzaldehyde (4.82 g, 33.9 mmol), 4-methylimidazole (5.57 g, 67.8 mmol), and K2CO3 (7.03 g, 50.9 mmol) were dissolved in 35 ml of DMF and stirred at 100° C. overnight. Cooled to room temperature and DMF removed in vacuo. The concentrated mass was taken up in EtOAc and water. Layers were separated and the aqueous layer was extracted twice with EtOAc. The organic extracts were combined, dried (Na2SO4), and concentrated. Chromatography on SiO2 (0-75% EtOAc/CH2Cl2) gave a cream-colored solid (mixture of isomers). This mass was taken up in a minimum amount of EtOH and treated with water until the formation of a precipitate. The precipitate was collected as a white solid and yielded 522.5 mg (2.6 mmol, 8%) after drying under high vacuum overnight. A solution of aldehyde intermediate (516 mg, 2.53 mmol) in 20 ml of MeOH was treated with K2CO3 (698 mg, 5.05 mmol) and a solution of dimethyl (1-diazo-2-oxopropyl)phosphonate (583 mg, 3.03 mmol) in 10 ml of MeOH and stirred at room temperature for 2.5 hours. MeOH was removed in vacuo and the concentrated mass was dissolved in aqueous NaHCO3 and EtOAc. Layers were separated and the aqueous layer was extracted twice with EtOAc. The organic extracts were combined, dried (Na2SO4), and concentrated to a yellow powder (506 mg, 2.5 mmol, 100%).

Workup

  1. temperatureCooled to room temperature
  2. customDMF removed in vacuo
  3. customLayers were separated
  4. extractionthe aqueous layer was extracted twice with EtOAc
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customChromatography on SiO2 (0-75% EtOAc/CH2Cl2) gave
  8. additiona cream-colored solid (mixture of isomers)
  9. customThe precipitate was collected as a white solid
  10. customyielded 522.5 mg (2.6 mmol, 8%)
  11. customafter drying under high vacuum overnight
  12. customMeOH was removed in vacuo
  13. dissolutionthe concentrated mass was dissolved in aqueous NaHCO3
  14. customLayers were separated
  15. extractionthe aqueous layer was extracted twice with EtOAc
  16. dry with materialdried (Na2SO4)

Sources & evidence

ORD record
ord-94ed4a331c3a454ea835d2b8cb96ab28
Source dataset
uspto-grants-2012_08
Patent number
US08242150B2

Reaction notes

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