Hydrochloric Acid → 3-[1-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]benzyl]-3-phenyl-1H-pyrazol-4-yl]propionic acid

HRID 350129Notes

Reaction equation

HRID 350129 reaction equation
[H-].[Na+].[C:3]1([C:9]2[C:13]([CH2:14][CH2:15][C:16]([O:18]CC)=[O:17])=[CH:12][NH:11][N:10]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl[CH2:22][C:23]1[CH:43]=[CH:42][C:26]([O:27][CH2:28][CH2:29][C:30]2[N:31]=[C:32]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[O:33][C:34]=2[CH3:35])=[CH:25][CH:24]=1.[OH-].[Na+].Cl>O1CCCC1.C(O)C.O.CN(C)C=O>[CH3:35][C:34]1[O:33][C:32]([C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)=[N:31][C:30]=1[CH2:29][CH2:28][O:27][C:26]1[CH:25]=[CH:24][C:23]([CH2:22][N:11]2[CH:12]=[C:13]([CH2:14][CH2:15][C:16]([OH:18])=[O:17])[C:9]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=3)=[N:10]2)=[CH:43][CH:42]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 118095944-[2-(4-Chloromethylphenoxy)ethyl]-5-methyl-2-phenyloxazoleHCID 178471160HCID 178471160, compound

Product 1

HCID 694226493-[1-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]benzyl]-3-phenyl-1H-pyrazol-4-yl]propionic acidYield 71%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (60%, oily, 200 mg) was added to an N,N-dimethylformamide solution (15 ml) of ethyl 3-(3-phenyl-1H-pyrazole-4-yl)propionate (1.04 g) at 0° C., which was stirred at 0° C. for 30 minutes. 4-[2-(4-Chloromethylphenoxy)ethyl]-5-methyl-2-phenyloxazole (1.43 g) was added to the reaction mixture, which was stirred at room temperature overnight. The reaction mixture was poured into water, which was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), then concentrated. The residue was subjected to silica gel column chromatography, and an oily substance was obtained from the fraction eluted with ethyl acetate-hexane (1:2, volume ratio). A mixture of the substance obtained, 1N aqueous sodium hydroxide solution (4 ml), ethanol (5 ml) and tetrahydrofuran (5 ml) was stirred for 2 hours at room temperature. The reaction mixture was acidified with dilute hydrochloric acid, which was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), then concentrated. The crystals obtained were collected by filtration to yield 3-[1-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]benzyl]-3-phenyl-1H-pyrazol-4-yl]propionic acid (930 mg, yield: 71%). This was recrystallized from acetone-hexane. Melting point: 142–143° C.

Workup

  1. stirringwas stirred at room temperature overnight
  2. extractionwas extracted with ethyl acetate
  3. washThe ethyl acetate layer was washed with saturated aqueous sodium chloride solution
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customan oily substance was obtained from the fraction
  7. washeluted with ethyl acetate-hexane (1:2, volume ratio)
  8. additionA mixture of the substance
  9. customobtained
  10. extractionwas extracted with ethyl acetate
  11. washThe ethyl acetate layer was washed with saturated aqueous sodium chloride solution
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated
  14. customThe crystals obtained
  15. filtrationwere collected by filtration

Sources & evidence

ORD record
ord-bb4535689a6a4eda96adb351577e9264
Source dataset
uspto-grants-2007_02
Patent number
US07179823B1

Reaction notes

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