Ethyl orthoformate → HCID 67252798, compound

HRID 2042119Notes

Reaction equation

HRID 2042119 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([N:10]3[C:14]([C:15]([OH:17])=[O:16])=[CH:13][C:12]([C:18](C)([CH3:20])[CH3:19])=[N:11]3)=[CH:9][C:4]=2[N:3]=[CH:2]1.C(OCC)(OCC)OCC.CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1>>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([N:10]3[C:14]([C:15]([OH:17])=[O:16])=[CH:13][C:12]([CH:18]([CH3:20])[CH3:19])=[N:11]3)=[CH:9][C:4]=2[N:3]=[CH:2]1

Participants

4

Reactant 3

HCID 31214Ethyl orthoformateHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 67254007HCID 67254007, compound

Product 1

HCID 67252798HCID 67252798, compoundYield 45%

Conditions

Temperature
140 °C

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. customThe solvent was evaporated
  2. additionthe residue was treated with methylene chloride
  3. filtrationThe resulting solid was filtered
  4. washwashed with methylene chloride

Sources & evidence

ORD record
ord-853616bc0081418bb02ff2eea71665f8
Source dataset
uspto-grants-2013_11
Patent number
US08586565B2

Reaction notes

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