3-Amino-p-cresol → N-(5-hydroxy-2-methylphenyl)-1,3-dimethyl-1H-pyrazole-5-carboxamide

HRID 1667824

Reaction equation

HRID 1667824 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[CH:6][C:7]=1[CH3:8].[CH3:10][N:11]1[C:15]([C:16](Cl)=[O:17])=[CH:14][C:13]([CH3:19])=[N:12]1.C(OCC)(=O)C.O1CCCC1.C(=O)([O-])O.[Na+]>CN(C)C(=O)C>[OH:9][C:4]1[CH:5]=[CH:6][C:7]([CH3:8])=[C:2]([NH:1][C:16]([C:15]2[N:11]([CH3:10])[N:12]=[C:13]([CH3:19])[CH:14]=2)=[O:17])[CH:3]=1

Participants

6

Reactant 4

HCID 178203-Amino-p-cresolHCID 516892Sodium BicarbonateHCID 27362992,5-Dimethyl-2H-pyrazole-3-carbonyl chlorideHCID 21939870Tetrahydrofuran ethyl acetate

Product 1

HCID 57505436N-(5-hydroxy-2-methylphenyl)-1,3-dimethyl-1H-pyrazole-5-carboxamideYield 63.6%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 3-amino-4-methylphenol (930 mg, 7.5 mmol) in N,N-dimethylacetamide (10 mL) was added a solution of 1,3-dimethyl-1H-pyrazole-5-carbonylchloride (1370 mg, 8.7 mmol) in N, N-dimethylacetamide (5 mL), and the mixture was stirred at 0° C. for 20 min. To the mixture were added ethyl acetate/tetrahydrofuran, saturated aqueous sodium hydrogencarbonate solution, and the aqueous layer was extracted 4 times with ethyl acetate/tetrahydrofuran. Combined organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and filtrated. The filtrate was concentrated under reduced pressure, and the residue was washed with ethyl acetate/hexane to give N-(5-hydroxy-2-methylphenyl)-1,3-dimethyl-1H-pyrazole-5-carboxamide (1170 mg, 63%) as a white solid. To a suspension of lithium aluminum hydride (1130 mg, 24 mmol) in tetrahydrofuran (35 mL) was slowly added dropwise a solution of N-(5-hydroxy-2-methylphenyl)-1,3-dimethyl-1H-pyrazole-5-carboxamide (1170 mg, 4.8 mmol) in tetrahydrofuran (10 mL) under ice-cooling. After dropwise addition, the reaction mixture was heated under reflux for 5 hr. A saturated aqueous sodium sulfate solution was added to the mixture under cooling, magnesium sulfate was added and the insoluble material was filtrated. The filtrate was concentrated under reduced pressure, and the residue was washed with ethyl acetate/hexane to give the title compound (570 mg, 52%) as a white solid.

Workup

  1. extractionthe aqueous layer was extracted 4 times with ethyl acetate/tetrahydrofuran
  2. washCombined organic layer was washed with water and saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltrated
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. washthe residue was washed with ethyl acetate/hexane

Sources & evidence

ORD record
ord-67c07569550a4ad48f26147b1d7e258b
Source dataset
uspto-grants-2011_10
Patent number
US08044049B2

Linked notes

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