Hydrochloric Acid → 3-(1,5-diphenyl-1H-pyrazol-4-yl)propionic acid

HRID 30703Notes

Reaction equation

HRID 30703 reaction equation
[C:1]1([N:7]2[C:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[C:10]([CH2:18]O)[CH:9]=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CS(Cl)(=O)=O.C(OCC)(=O)[CH2:26][C:27]([O:29]CC)=[O:28].[Na].Cl>CN(C)C=O.C(O)(=O)C.C(OCC)(=O)C.C(N(CC)CC)C>[C:1]1([N:7]2[C:11]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)=[C:10]([CH2:18][CH2:26][C:27]([OH:29])=[O:28])[CH:9]=[N:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

9

Reactant 4

HCID 313Hydrochloric Acid2×HCID 31297Methanesulfonyl chlorideHCID 21770110HCID 21770110, compoundHCID 86602522HCID 86602522, compound

Product 1

HCID 692088203-(1,5-diphenyl-1H-pyrazol-4-yl)propionic acidYield 68%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent2×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of (1,5-diphenyl-1H-pyrazol-4-yl)methanol (11.78 g), triethylamine (10 ml) and ethyl acetate (300 ml) was added dropwise methanesulfonyl chloride (4.5 ml) at 0° C. The mixture was stirred at room temperature for 1 hr. and the ethyl acetate layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated to give an oil. This oil was dissolved in N,N-dimethylformamide (100 ml) and the resulting solution was added dropwise to a solution of sodium diethyl malonate in N,N-dimethylformamide (prepared using diethyl malonate 20.33 g, sodium hydride (60% in oil, 4.88 g) and N,N-dimethylformamide 200 ml) at 0° C. The mixture was stirred at room temperature for 5 hrs., and poured into a 1N aqueous hydrochloric acid solution. The mixture was extracted with ethyl acetate. The ethyl acetate layer was washed successively with a 1N aqueous hydrochloric acid solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated to give an oil. A mixture of this oil, a 6N aqueous hydrochloric acid solution (100 ml) and acetic acid (50 ml) was heated under reflux for 5 hrs. The reaction mixture was cooled, concentrated and poured into water. The precipitated crystals were collected by filtration, washed with water, and dried to give 3-(1,5-diphenyl-1H-pyrazol-4-yl)propionic acid. yield: 68%. colorless needle crystals. melting point: 159-160° C. (recrystallized from acetone-hexane).

Workup

  1. washand the ethyl acetate layer was washed successively with water and saturated brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. concentrationconcentrated
  4. customto give an oil
  5. stirringThe mixture was stirred at room temperature for 5 hrs
  6. extractionThe mixture was extracted with ethyl acetate
  7. washThe ethyl acetate layer was washed successively with a 1N aqueous hydrochloric acid solution and saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated
  10. customto give an oil
  11. additionA mixture of this oil
  12. temperatureunder reflux for 5 hrs
  13. temperatureThe reaction mixture was cooled
  14. concentrationconcentrated
  15. additionpoured into water
  16. filtrationThe precipitated crystals were collected by filtration
  17. washwashed with water
  18. customdried

Sources & evidence

ORD record
ord-a7d042719edc4385b48ebd6a24c8afaa
Source dataset
uspto-grants-2008_09
Patent number
US07423159B2

Reaction notes

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