Ethylene Glycol → HCID 57585847, compound

HRID 547648Notes

Reaction equation

HRID 547648 reaction equation
[F:1][C:2]([F:26])([F:25])[C:3]([NH:5][C:6]1[CH:11]=[C:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([CH:19]=[O:20])=[CH:15][CH:14]=2)[CH:9]=[C:8]([F:21])[C:7]=1[N+:22]([O-])=O)=O.C(OCC)(OCC)OCC.C(O)CO>C(OCC)(=O)C>[F:21][C:8]1[C:7]2[N:22]=[C:3]([C:2]([F:26])([F:25])[F:1])[NH:5][C:6]=2[CH:11]=[C:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([CH:19]=[O:20])=[CH:15][CH:14]=2)[CH:9]=1

Participants

5

Reactant 3

HCID 174Ethylene GlycolHCID 31214Ethyl orthoformateHCID 57585858HCID 57585858, compound

Product 1

HCID 57585847HCID 57585847, compoundYield 14%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 2,2,2-trifluoro-N-{3-fluoro-5-[(4-formylphenyl)oxy]-2-nitrophenyl}acetamide (1.25 g, 3.36 mmol), triethyl orthoformate (0.614 mL, 3.69 mmol), and ethylene glycol (0.749 g, 13.43 mmol) was added Bu4NBr3 (0.016 g, 0.034 mmol). The homogeneous reaction was stirred at ambient temperature for 1 hour and then diluted with ethyl acetate. The organics were washed 1×NaHCO3, once in brine and then dried (Na2SO4), filtered and concentrated with no further purification necessary. Residue (0.400 g) was re-dissolved in ethyl acetate (5 mL) and hydrogenated using 10% palladium on carbon (0.080 g) under an atmosphere of hydrogen for 16 hours. The catalyst was removed by filtration through Celite and the filtrate concentrated. The residue was re-dissolved in acetone and MP-Fosic acid resin (1.26 g, 1.92 mmol) was added. The mixture was stirred for 16 hours, filtered and the filtrate was concentrated. Chromatography on silica using 40% ethyl acetate/hexanes eluted the product to give 0.153 g of 4-{[4-fluoro-2-(trifluoromethyl)-1H-benzimidazol-6-yl]oxy}benzaldehyde as an off-white solid.

Workup

  1. additionwas added Bu4NBr3 (0.016 g, 0.034 mmol)
  2. customThe homogeneous reaction
  3. washThe organics were washed 1×NaHCO3
  4. dry with materialonce in brine and then dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated with no further purification necessary
  7. dissolutionResidue (0.400 g) was re-dissolved in ethyl acetate (5 mL)
  8. customfor 16 hours
  9. customThe catalyst was removed by filtration through Celite
  10. concentrationthe filtrate concentrated
  11. dissolutionThe residue was re-dissolved in acetone
  12. stirringThe mixture was stirred for 16 hours
  13. filtrationfiltered
  14. concentrationthe filtrate was concentrated
  15. washChromatography on silica using 40% ethyl acetate/hexanes eluted the product

Sources & evidence

ORD record
ord-76f2cc75cd4e4403a763f01834d50459
Source dataset
uspto-grants-2011_05
Patent number
US07939528B2

Reaction notes

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