Hydrochloric Acid → 1-(4-Methoxybenzyl)-1H-pyrazole-3,5-dicarboxylic Acid

HRID 882567Notes

Reaction equation

HRID 882567 reaction equation
[NH:1]1[C:5]([C:6]([O:8]CC)=[O:7])=[CH:4][C:3]([C:11]([O:13]CC)=[O:12])=[N:2]1.C([O-])([O-])=O.[K+].[K+].[CH3:22][O:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28]Cl)=[CH:26][CH:25]=1.[OH-].[Na+].Cl>CN(C=O)C.C1COCC1.O.CCOC(C)=O>[CH3:22][O:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][N:1]2[C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]([C:11]([OH:13])=[O:12])=[N:2]2)=[CH:26][CH:25]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 699934-Methyloxybenzyl chlorideHCID 142184diethyl 1H-pyrazole-3,5-dicarboxylate

Product 1

HCID 710741191-(4-Methoxybenzyl)-1H-pyrazole-3,5-dicarboxylic Acid

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Diethyl 3,5-pyrazoledicarboxylate (400 mg, 1.9 mmol, 1.0 eq.) and K2CO3 (391 mg, 2.8 mmol, 1.5 eq.) were dissolved in DMF (1.50 mL) with stirring. p-Methoxybenzyl chloride (295 mg, 1.9 mmol, 1.0 eq.) was added and the mixture was stirred at room temperature overnight. EtOAc (20 mL) and water (20 mL) were added. The organic fractions were separated and washed with water (20 mL) and saturated aqueous NaCl (20 mL), dried over Na2SO4, The solvent was removed to yield a clear oil, which was purified by flash chromatography (0-40% EtOAc/hexanes over 20 minutes). The fractions were combined and the solvent evaporated. THF (7 mL) and 2M aqueous NaOH (3.8 mL, 4.0 eq.) was added and the mixture stirred at room temperature overnight. The mixture was acidified with 1N HCl to pH˜4. The precipitate was filtered off and dried under vacuum to yield the title compound as a white solid. (440 mg).

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. customThe organic fractions were separated
  3. washwashed with water (20 mL) and saturated aqueous NaCl (20 mL)
  4. dry with materialdried over Na2SO4
  5. customThe solvent was removed
  6. customto yield a clear oil, which
  7. customwas purified by flash chromatography (0-40% EtOAc/hexanes over 20 minutes)
  8. customthe solvent evaporated
  9. stirringthe mixture stirred at room temperature overnight
  10. filtrationThe precipitate was filtered off
  11. customdried under vacuum

Sources & evidence

ORD record
ord-467c14cf6bbd4fdebed9e2b97b66a1ee
Source dataset
uspto-grants-2015_03
Patent number
US08993752B2

Reaction notes

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