Ethyl orthoformate → HCID 67252798, compound

HRID 1711699Notes

Reaction equation

HRID 1711699 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-aa9df50b63194bc7a7fe8501d56b7ba3
Source dataset
uspto-grants-2010_09
Patent number
US07790756B2

Reaction notes

Loading…