Water → HCID 69421854, compound

HRID 350168Notes

Reaction equation

HRID 350168 reaction equation
[OH:1][C:2]1[C:6]([CH2:7][CH2:8][C:9]([O:11]CC)=[O:10])=[CH:5][N:4]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]3[N:24]=[C:25]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[O:26][C:27]=3[CH3:28])=[CH:17][CH:16]=2)[N:3]=1.[H-].[Na+].Cl[C:38]1[CH:43]=[CH:42][C:41]([C:44]([F:47])([F:46])[F:45])=[CH:40][N:39]=1.O>CN(C)C=O>[CH3:28][C:27]1[O:26][C:25]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[N:24][C:23]=1[CH2:22][O:21][C:18]1[CH:19]=[CH:20][C:15]([CH2:14][N:4]2[CH:5]=[C:6]([CH2:7][CH2:8][C:9]([OH:11])=[O:10])[C:2]([O:1][C:38]3[CH:43]=[CH:42][C:41]([C:44]([F:47])([F:46])[F:45])=[CH:40][N:39]=3)=[N:3]2)=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 923422-Chloro-5-(trifluoromethyl)pyridineHCID 178471113HCID 178471113, compound

Product 1

HCID 69421854HCID 69421854, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of ethyl 3-[3-hydroxy-1-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-1H-pyrazol-4-yl]propionate (1.00 g) in N,N-dimethylformamide (80 ml), sodium hydride (60%, oily, 100 mg) was added at 0° C., and the solution was stirred at room temperature for 30 minutes. 2-Chloro-5-trifluoromethylpyridine (0.45 g) was added to the reaction mixture, which was stirred at 90° C. for two hours. 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 (1:1, volume ratio). A mixture of the obtained oily substance, 1 N aqueous sodium hydroxide solution (5 ml), tetrahydrofuran (5 ml), and ethanol (10 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-[1-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-3-(5-trifluoromethyl-2-pyridyloxy)-1H-pyrazol-4-yl]propionic acid was obtained (960 mg, yield: 76%). This was recrystallized from ethyl acetate-hexane. Melting point: 107–108° C.

Workup

  1. stirringwas stirred at 90° C. for two hours
  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 (1:1, volume ratio)
  8. additionA mixture of the obtained oily substance, 1 N aqueous sodium hydroxide solution (5 ml), tetrahydrofuran (5 ml), and ethanol (10 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-2a06539eac094438a73319bd76635001
Source dataset
uspto-grants-2007_02
Patent number
US07179823B1

Reaction notes

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