Dimethylformamide → HCID 11691261, compound

HRID 350192Notes

Reaction equation

HRID 350192 reaction equation
[CH2:1]([O:3][C:4]1[C:8]([CH2:9][CH2:10][C:11]([O:13]CC)=[O:12])=[CH:7][NH:6][N:5]=1)[CH3:2].Cl[CH2:17][C:18]1[CH:36]=[CH:35][C:21]([O:22][CH2:23][C:24]2[N:25]=[C:26]([C:30]3[S:31][CH:32]=[CH:33][CH:34]=3)[O:27][C:28]=2[CH3:29])=[CH:20][CH:19]=1.CN(C)C=O.[H-].[Na+]>O>[CH2:1]([O:3][C:4]1[C:8]([CH2:9][CH2:10][C:11]([OH:13])=[O:12])=[CH:7][N:6]([CH2:17][C:18]2[CH:19]=[CH:20][C:21]([O:22][CH2:23][C:24]3[N:25]=[C:26]([C:30]4[S:31][CH:32]=[CH:33][CH:34]=4)[O:27][C:28]=3[CH3:29])=[CH:35][CH:36]=2)[N:5]=1)[CH3:2]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 23021914HCID 23021914, compoundHCID 178471163HCID 178471163, compound

Product 1

HCID 11691261HCID 11691261, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture of ethyl 3-(3-ethoxy-1H-pyrazole-4-yl]propionate (300 mg), 4-(4-chloromethylphenoxymethyl)-5-methyl-2-(2-thienyl)oxazole (450 mg), and N,N-dimethylformamide (5 ml), sodium hydride (60%, oily, 70.0 mg) was added at 0° C., and then the mixture was stirred at room temperature for 30 minutes. The reaction mixture was poured into water, which was extracted with ethyl acetate. The ethyl acetate layer was washed with water, then, with saturated aqueous sodium chloride solution, and dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and a colorless oily substance was obtained from the fraction eluted with ethyl acetate-hexane (1:2, volume ratio). A mixture of the obtained colorless oily substances, 1 N aqueous sodium hydroxide solution (5 ml), tetrahydrofuran (5 ml), and ethanol (5 ml) was stirred at room temperature overnight, diluted with 1 N hydrochloric acid (5 ml), and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), and concentrated. The obtained colorless crystals were collected by filtration, and 3-[3-ethoxy-1-[4-[5-methyl-2-(2-thienyl)-4-oxazolylmethoxy]benzyl]-1H-pyrazol-4-yl]propionic acid (460 mg, yield: 70%) was obtained. This was recrystallized from acetone-hexane. Melting point: 156–157° C.

Workup

  1. additionwas added at 0° C.
  2. extractionwas extracted with ethyl acetate
  3. washThe ethyl acetate layer was washed with water
  4. dry with materialwith saturated aqueous sodium chloride solution, and dried (MgSO4)
  5. concentrationconcentrated
  6. customa colorless oily substance was obtained from the fraction
  7. washeluted with ethyl acetate-hexane (1:2, volume ratio)
  8. additionA mixture of the obtained colorless oily substances, 1 N aqueous sodium hydroxide solution (5 ml), tetrahydrofuran (5 ml), and ethanol (5 ml)
  9. stirringwas stirred at room temperature overnight
  10. additiondiluted with 1 N hydrochloric acid (5 ml)
  11. extractionextracted with ethyl acetate
  12. washThe ethyl acetate layer was washed with saturated aqueous sodium chloride solution
  13. dry with materialdried (MgSO4)
  14. concentrationconcentrated
  15. filtrationThe obtained colorless crystals were collected by filtration

Sources & evidence

ORD record
ord-c27981a2d57b404db8caf4b828feec4e
Source dataset
uspto-grants-2007_02
Patent number
US07179823B1

Reaction notes

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