4-Hydroxybenzaldehyde → HCID 57585865, compound

HRID 547650Notes

Reaction equation

HRID 547650 reaction equation
[F:1][C:2]1[C:3]([N+:10]([O-:12])=[O:11])=[C:4]([CH:6]=[C:7](F)[CH:8]=1)[NH2:5].[C:13]([O-:16])([O-])=O.[Cs+].[Cs+].[OH:19][C:20]1[CH:27]=[CH:26][C:23]([CH:24]=[O:25])=[CH:22][CH:21]=1.O>CS(C)=O>[F:1][C:2]1[C:3]([N+:10]([O-:12])=[O:11])=[C:4]([NH:5][CH:13]=[O:16])[CH:6]=[C:7]([O:19][C:20]2[CH:27]=[CH:26][C:23]([CH:24]=[O:25])=[CH:22][CH:21]=2)[CH:8]=1

Participants

6

Reactant 4

HCID 1264-HydroxybenzaldehydeHCID 962WaterHCID 10796Cesium carbonateHCID 2230923,5-difluoro-2-nitroaniline

Product 1

HCID 57585865HCID 57585865, compoundYield 37.8%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of the 3,5-difluoro-2-nitroaniline (0.348 g, 2.0 mmol), Cs2CO3 (1.63 g, 5 mmol), and 4-hydroxybenzaldehyde (0.268 g, 2.2 mmol) in dimethylsulfoxide (2 mL) was heated to 80 degrees Centigrade for 1 hour and then cooled. Water was added and the organics extracted using ethyl acetate (2×50 mL). The combined organics were then washed once in brine and dried (Na2SO4), filtered and concentrated. Chromatography on silica gel (gradient of 20%-60% ethyl acetate/hexanes) eluted the product and the fractions were concentrated. The residue was refluxed in 96% formic acid (4 mL) until the reaction was complete conversion of the aniline was observed by TLC (−1.5 h) and then cooled and poured onto ice-water. The organics were extracted with ethyl acetate (2×25 mL) and the combined organics washed once in water, once in brine, dried (Na2SO4), filtered and concentrated to give 0.230 g of the {3-fluoro-5-[(4-formylphenyl)oxy]-2-nitrophenyl}formamide as a solid.

Workup

  1. temperaturecooled
  2. extractionthe organics extracted
  3. washThe combined organics were then washed once in brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. washChromatography on silica gel (gradient of 20%-60% ethyl acetate/hexanes) eluted the product
  8. concentrationthe fractions were concentrated
  9. temperatureThe residue was refluxed in 96% formic acid (4 mL) until the reaction
  10. customwas observed by TLC (−1.5 h)
  11. temperaturecooled
  12. additionpoured onto ice-water
  13. extractionThe organics were extracted with ethyl acetate (2×25 mL)
  14. washthe combined organics washed once in water, once in brine
  15. dry with materialdried (Na2SO4)
  16. filtrationfiltered
  17. concentrationconcentrated

Sources & evidence

ORD record
ord-c97ef95257154fedbdfcf5d7d46edd68
Source dataset
uspto-grants-2011_05
Patent number
US07939528B2

Reaction notes

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