Dimethylformamide → 3-[3-ethoxy-1-[4-(2-quinolylmethoxy)benzyl]-1H-pyrazol-4-yl]propionic acid

HRID 350210

Reaction equation

HRID 350210 reaction equation
[CH2:1]([O:3][C:4]1[C:8]([CH2:9][CH2:10][C:11]([O:13]CC)=[O:12])=[CH:7][N:6]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=2)[N:5]=1)[CH3:2].Cl.Cl[CH2:26][C:27]1[CH:36]=[CH:35][C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[N:28]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH2:1]([O:3][C:4]1[C:8]([CH2:9][CH2:10][C:11]([OH:13])=[O:12])=[CH:7][N:6]([CH2:16][C:17]2[CH:18]=[CH:19][C:20]([O:23][CH2:26][C:27]3[CH:36]=[CH:35][C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[N:28]=3)=[CH:21][CH:22]=2)[N:5]=1)[CH3:2]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 30838232-(Chloromethyl)quinoline hydrochlorideHCID 23024904ethyl 3-[3-ethoxy-1-(4-hydroxybenzyl)-1H-pyrazol-4-yl]propionate

Product 1

HCID 694228233-[3-ethoxy-1-[4-(2-quinolylmethoxy)benzyl]-1H-pyrazol-4-yl]propionic acidYield 86.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of ethyl 3-[3-ethoxy-1-(4-hydroxybenzyl)-1H-pyrazol-4-yl]propionate (360 mg), 2-chloromethylquinoline hydrochloride (270 mg), potassium carbonate (300 mg) and N,N-dimethylformamide (10 ml) was stirred at 80° C. for 5 hours. The reaction mixture was poured into water, and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), and concentrated. The residue was subjected to silica gel column chromatography to obtain a colorless oily substance from the fraction eluted with ethyl acetate-hexane (1:1, volume ratio). After a mixture of the resulting oily substance, 1N aqueous sodium hydroxide solution (5 ml), tetrahydrofuran (5 ml) and ethanol (5 ml) was stirred at room temperature for 2 hours, 1N hydrochloric acid (5 ml) was added to the mixture, and then the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4) and concentrated. The resulting colorless crystals were collected by filtration to obtain 3-[3-ethoxy-1-[4-(2-quinolylmethoxy)benzyl]-1H-pyrazol-4-yl]propionic acid (420 mg, yield: 86%). This was recrystallized from acetone-hexane. Melting point: 140–141° C.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe ethyl acetate layer was washed with saturated aqueous sodium chloride solution
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customto obtain a colorless oily substance from the fraction
  6. washeluted with ethyl acetate-hexane (1:1, volume ratio)
  7. additionAfter a mixture of the resulting oily substance, 1N aqueous sodium hydroxide solution (5 ml), tetrahydrofuran (5 ml) and ethanol (5 ml)
  8. stirringwas stirred at room temperature for 2 hours
  9. addition1N hydrochloric acid (5 ml) was added to the mixture
  10. extractionthe mixture was 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. filtrationThe resulting colorless crystals were collected by filtration

Sources & evidence

ORD record
ord-9aa8e20c878242cb9ccad44b6e39fce8
Source dataset
uspto-grants-2007_02
Patent number
US07179823B1

Linked notes

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