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

HRID 350321Notes

Reaction equation

HRID 350321 reaction equation
[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:43]=[CH:42][C:18]([CH2:19][N:20]2[CH:24]=[C:23]([CH2:25][CH:26](C(OCC)=O)[C:27]([O:29]CC)=[O:28])[C:22]([C:37]3[S:38][CH:39]=[CH:40][CH:41]=3)=[N:21]2)=[CH:17][CH:16]=1.[OH-].[Na+].Cl>C(O)C>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:43]=[CH:42][C:18]([CH2:19][N:20]2[CH:24]=[C:23]([CH2:25][CH2:26][C:27]([OH:29])=[O:28])[C:22]([C:37]3[S:38][CH:39]=[CH:40][CH:41]=3)=[N:21]2)=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 70125202diethyl [1-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-3-(2-thienyl)-1H-pyrazol-4-yl]methylmalonate

Product 1

HCID 102071433-[1-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-3-(2-thienyl)-1H-pyrazol-4-yl]propionic acidYield 80%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of diethyl [1-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-3-(2-thienyl)-1H-pyrazol-4-yl]methylmalonate (6.08 g), 4N sodium hydroxide solution (10 ml), and ethanol (10 ml) was refluxed for 1 hour. After cooling, 1N hydrochloric acid (40 ml) was added to the mixture, and 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 oily substance was dissolved in pyridine (50 ml), and stirred at 110° C. for 2 hours. After pyridine was removed under reduced pressure, ethyl acetate was added to the residue. The resulting solution was washed successively with dilute hydrochloric acid and saturated aqueous sodium chloride solution, dried (MgSO4), and concentrated. The resulting colorless crystals were collected by filtration to obtain 3-[1-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-3-(2-thienyl)-1H-pyrazol-4-yl]propionic acid (4.02 g, yield: 80%). This was recrystallized from acetone-hexane. Melting point: 172˜173° C.

Workup

  1. temperaturewas refluxed for 1 hour
  2. temperatureAfter cooling
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe ethyl acetate layer was washed with saturated aqueous sodium chloride solution
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. dissolutionThe resulting colorless oily substance was dissolved in pyridine (50 ml)
  8. customAfter pyridine was removed under reduced pressure, ethyl acetate
  9. additionwas added to the residue
  10. washThe resulting solution was washed successively with dilute hydrochloric acid and saturated aqueous sodium chloride solution
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated
  13. filtrationThe resulting colorless crystals were collected by filtration

Sources & evidence

ORD record
ord-6f09215d0f2f4d7badbad28505c250a8
Source dataset
uspto-grants-2007_02
Patent number
US07179823B1

Reaction notes

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