Dimethylformamide → 3-[4-({4-[({4-[(E)-2-(diethoxyphosphoryl)ethenyl]-1-phenyl-1H-pyrazol-3-yl}oxy)methyl]phenoxy}methyl)-5-methyl-1,3-oxazol-2-yl]benzoic acid

HRID 2221920Notes

Reaction equation

HRID 2221920 reaction equation
[CH:1]([C:3]1[C:4]([O:14][CH2:15][C:16]2[CH:39]=[CH:38][C:19]([O:20][CH2:21][C:22]3[N:23]=[C:24]([C:28]4[CH:29]=[C:30]([CH:35]=[CH:36][CH:37]=4)[C:31]([O:33]C)=[O:32])[O:25][C:26]=3[CH3:27])=[CH:18][CH:17]=2)=[N:5][N:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:7]=1)=O.[CH2:40](P(=O)(OCC)OCC)[P:41](=[O:48])([O:45][CH2:46][CH3:47])[O:42][CH2:43][CH3:44].CN(C)C=O.[H-].[Na+]>O>[CH2:43]([O:42][P:41](/[CH:40]=[CH:1]/[C:3]1[C:4]([O:14][CH2:15][C:16]2[CH:17]=[CH:18][C:19]([O:20][CH2:21][C:22]3[N:23]=[C:24]([C:28]4[CH:29]=[C:30]([CH:35]=[CH:36][CH:37]=4)[C:31]([OH:33])=[O:32])[O:25][C:26]=3[CH3:27])=[CH:38][CH:39]=2)=[N:5][N:6]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:7]=1)([O:45][CH2:46][CH3:47])=[O:48])[CH3:44]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 15455Tetraethyl methylenediphosphonateHCID 24758Sodium hydrideHCID 86605863methyl 3-{4-[(4-{[(4-formyl-1-phenyl-1H-pyrazol-3-yl)oxy]methyl}phenoxy)methyl]-5-methyl-1,3-oxazol-2-yl}benzoate

Product 1

HCID 866058623-[4-({4-[({4-[(E)-2-(diethoxyphosphoryl)ethenyl]-1-phenyl-1H-pyrazol-3-yl}oxy)methyl]phenoxy}methyl)-5-methyl-1,3-oxazol-2-yl]benzoic acidYield 88%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture of methyl 3-{4-[(4-{[(4-formyl-1-phenyl-1H-pyrazol-3-yl)oxy]methyl}phenoxy)methyl]-5-methyl-1,3-oxazol-2-yl}benzoate (0.29 g), tetraethyl methylenediphosphonate (0.18 g) and N,N-dimethylformamide (10 mL) was added sodium hydride (60% in oil, 0.03 g) at room temperature, and the mixture was stirred at the same temperature for 15 hrs. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography to give an oily substance (0.28 g) from a fraction eluted with ethyl acetate-hexane (8:1, v/v). To a mixture of the oily substance, tetrahydrofuran (2 mL) and methanol (2 mL) was added 1N aqueous sodium hydroxide solution (2 mL), and the mixture was stirred at 60° C. for 1 hr. To the reaction mixture was added dilute hydrochloric acid to acidify the solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated to give 3-[4-({4-[({4-[(E)-2-(diethoxyphosphoryl)ethenyl]-1-phenyl-1H-pyrazol-3-yl}oxy)methyl]phenoxy}methyl)-5-methyl-1,3-oxazol-2-yl]benzoic acid as colorless crystals (0.23 g, yield 88%). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 153-155° C.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated
  5. customto give an oily substance (0.28 g) from a fraction
  6. washeluted with ethyl acetate-hexane (8:1
  7. additionTo a mixture of the oily substance, tetrahydrofuran (2 mL) and methanol (2 mL)
  8. additionwas added 1N aqueous sodium hydroxide solution (2 mL)
  9. stirringthe mixture was stirred at 60° C. for 1 hr
  10. additionTo the reaction mixture was added dilute hydrochloric acid
  11. extractionthe mixture was extracted with ethyl acetate
  12. washThe organic layer was washed with saturated brine
  13. dry with materialdried over anhydrous magnesium sulfate
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-1ac4778fead047d88b3062bae16db9ef
Source dataset
uspto-grants-2008_05
Patent number
US07368578B2

Reaction notes

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