Dimethylformamide → diethyl (E)-2-{3-[(4-{[2-(3-hydroxyphenyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-3-methoxybenzyl)oxy]-1-phenyl-1H-pyrazol-4-yl}ethenylphosphonate

HRID 2221913Notes

Reaction equation

HRID 2221913 reaction equation
CS([O:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]2[O:13][C:14]([CH3:42])=[C:15]([CH2:17][O:18][C:19]3[CH:24]=[CH:23][C:22]([CH2:25][O:26][C:27]4[C:31]([CH:32]=O)=[CH:30][N:29]([C:34]5[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=5)[N:28]=4)=[CH:21][C:20]=3[O:40][CH3:41])[N:16]=2)[CH:7]=1)(=O)=O.[CH2:43]([P:52](=[O:59])([O:56][CH2:57][CH3:58])[O:53][CH2:54][CH3:55])P(=O)(OCC)OCC.CN(C)C=O.[H-].[Na+]>O>[OH:5][C:6]1[CH:7]=[C:8]([C:12]2[O:13][C:14]([CH3:42])=[C:15]([CH2:17][O:18][C:19]3[CH:24]=[CH:23][C:22]([CH2:25][O:26][C:27]4[C:31](/[CH:32]=[CH:43]/[P:52](=[O:59])([O:53][CH2:54][CH3:55])[O:56][CH2:57][CH3:58])=[CH:30][N:29]([C:34]5[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=5)[N:28]=4)=[CH:21][C:20]=3[O:40][CH3:41])[N:16]=2)[CH:9]=[CH:10][CH:11]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 15455Tetraethyl methylenediphosphonateHCID 24758Sodium hydrideHCID 866058573-{4-[(4-{[(4-formyl-1-phenyl-1H-pyrazol-3-yl)oxy]methyl}-2-methoxyphenoxy)methyl]-5-methyl-1,3-oxazol-2-yl}phenyl methanesulfonate

Product 1

HCID 86605856diethyl (E)-2-{3-[(4-{[2-(3-hydroxyphenyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-3-methoxybenzyl)oxy]-1-phenyl-1H-pyrazol-4-yl}ethenylphosphonateYield 15.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture of 3-{4-[(4-{[(4-formyl-1-phenyl-1H-pyrazol-3-yl)oxy]methyl}-2-methoxyphenoxy)methyl]-5-methyl-1,3-oxazol-2-yl}phenyl methanesulfonate (0.30 g), tetraethyl methylenediphosphonate (0.16 g) and N,N-dimethylformamide (10 mL) was added sodium hydride (60% in oil, 0.025 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 crystals from a fraction eluted with ethyl acetate-hexane (5:1, v/v). To a mixture of the obtained crystal, tetrahydrofuran (2 mL) and ethanol (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. The residue was subjected to silica gel column chromatography to give diethyl (E)-2-{3-[(4-{[2-(3-hydroxyphenyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-3-methoxybenzyl)oxy]-1-phenyl-1H-pyrazol-4-yl}ethenylphosphonate as colorless crystals (0.050 g, yield 15%) from a fraction eluted with ethyl acetate-hexane (8:1, v/v). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 127-128° 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 crystals from a fraction
  6. washeluted with ethyl acetate-hexane (5:1
  7. additionTo a mixture of the obtained crystal, tetrahydrofuran (2 mL) and ethanol (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-75492b058d08401b995ad35fa86f6b6c
Source dataset
uspto-grants-2008_05
Patent number
US07368578B2

Reaction notes

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