tert-butyl 1-(4-hydroxy-3-nitrophenyl)-3-isopropyl-1H-pyrazole-5-carboxylate → tert-butyl 1-(3-amino-4-hydroxyphenyl)-3-isopropyl-1H-pyrazole-5-carboxylate

HRID 2042118Notes

Reaction equation

HRID 2042118 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[CH:11][C:10]([CH:20]([CH3:22])[CH3:21])=[N:9]2)=[CH:4][C:3]=1[N+:23]([O-])=O>C(OCC)(=O)C.CO.[Pd]>[NH2:23][C:3]1[CH:4]=[C:5]([N:8]2[C:12]([C:13]([O:15][C:16]([CH3:18])([CH3:17])[CH3:19])=[O:14])=[CH:11][C:10]([CH:20]([CH3:22])[CH3:21])=[N:9]2)[CH:6]=[CH:7][C:2]=1[OH:1]

Participants

4

Reactant 1

HCID 67253892tert-butyl 1-(4-hydroxy-3-nitrophenyl)-3-isopropyl-1H-pyrazole-5-carboxylate

Product 1

HCID 67252991tert-butyl 1-(3-amino-4-hydroxyphenyl)-3-isopropyl-1H-pyrazole-5-carboxylate

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 21584119Ethylacetate methanolSolvent

Procedure

To a solution of tert-butyl 1-(4-hydroxy-3-nitrophenyl)-3-isopropyl-1H-pyrazole-5-carboxylate (0.27 g, 0.78 mmol) in ethyl acetate/methanol (1:1, 10 mL) was added palladium on carbon (30 mg) and the mixture was hydrogenated (50 psi) overnight under Parr. The solution was filtered and washed with methanol. The combined filtrate was concentrated to afford tert-butyl 1-(3-amino-4-hydroxyphenyl)-3-isopropyl-1H-pyrazole-5-carboxylate. The crude tert-butyl 1-(3-amino-4-hydroxyphenyl)-3-isopropyl-1H-pyrazole-5-carboxylate was treated with 25% TFA in CH2Cl2 (2 mL) and stirred overnight at RT. The solvent was evaporated to obtain 1-(benzo[d]oxazol-5-yl)-3-tert-butyl-1H-pyrazole-5-carboxylic acid. To a solution of 1-(benzo[d]oxazol-5-yl)-3-tert-butyl-1H-pyrazole-5-carboxylic acid in xylenes (3 mL) was added triethyl orthoformate (0.16 mL, 0.96 mmol) and a catalytic amount of PPTS. The reaction mixture was heated at 140° C. for 4 hours. The solvent was evaporated and the residue was treated with methylene chloride with stirring for 1 hour. The resulting solid was filtered and washed with methylene chloride to obtain 1-(benzo[d]oxazol-5-yl)-3-isopropyl-1H-pyrazole-5-carboxylic acid (0.1 g, 45% yield: for three steps). MS (ESI) m/z: 272.0 (M+H+).

Workup

  1. custom(50 psi) overnight
  2. filtrationThe solution was filtered
  3. washwashed with methanol
  4. concentrationThe combined filtrate was concentrated

Sources & evidence

ORD record
ord-ced447eb5a2c46a3944c00eda0a13c8c
Source dataset
uspto-grants-2013_11
Patent number
US08586565B2

Reaction notes

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