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 1711698Notes

Reaction equation

HRID 1711698 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-19cbc69edc1342da8b3bb8ac064a98ee
Source dataset
uspto-grants-2010_09
Patent number
US07790756B2

Reaction notes

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