Hydrochloric Acid → 4-Methyl-3-pyrazol-1-yl-benzoic acid ethyl ester

HRID 491849Notes

Reaction equation

HRID 491849 reaction equation
[NH:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[CH3:12])[C:6]([OH:8])=[O:7])[NH2:2].[CH3:13][CH:14]([CH3:18])C(O)=O.[CH:19](=O)[CH2:20]C=O.Cl.[OH-].[Na+]>CCO>[CH2:19]([O:7][C:6](=[O:8])[C:5]1[CH:9]=[CH:10][C:11]([CH3:12])=[C:3]([N:1]2[CH:18]=[CH:14][CH:13]=[N:2]2)[CH:4]=1)[CH3:20]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 5551383-Hydrazino-4-methylbenzoic acidHCID 21097364Malonaldehyde(bismethylacetate)

Product 1

HCID 588613364-Methyl-3-pyrazol-1-yl-benzoic acid ethyl esterYield 47.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 3-hydrazino-4-methyl benzoic acid (1.0 g, 4.93 mmol), malonaldehyde(bismethylacetate) (0.82 mL, 4.93 mmol), and concentrated HCl (1 mL) in EtOH (20 mL) was heated to reflux for 4 h. After cooling to room temperature, the reaction was poured into ice water, neutralized with 2N NaOH, and extracted with CH2Cl2 (3×). The organic layers were dried over Na2SO4, filtered and concentrated to afford 4-methyl-3-pyrazol-1-yl-benzoic acid ethyl ester (536 mg, 47%) as a yellow oil. A solution of the pyrazole (536 mg, 2.33 mmol) and bromine (0.167 mL, 3.26 mmol) in CHCl3 (15 mL) was refluxed for 4.5 h then cooled to room temperature. The solvent was evaporated to an orange oil. Purification using chromatography on silica gel (1:1 EtOAc/hexanes) yielded 3-(4-bromo-pyrazol-1-yl)-4-methyl-benzoic acid ethyl ester (0.739 g, 99%) as a yellow solid.

Workup

  1. temperatureto reflux for 4 h
  2. extractionextracted with CH2Cl2 (3×)
  3. dry with materialThe organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-5f7d10e33d5b4d1393ada7daaad49a54
Source dataset
uspto-grants-2009_05
Patent number
US07531560B2

Reaction notes

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