Hydrochloric Acid → 4-(5-amino-3-tert-butyl-1H-pyrazol-1-yl)-2-methoxybenzoic acid

HRID 571093Notes

Reaction equation

HRID 571093 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:12]=[C:11]([NH:13][NH2:14])[CH:10]=[CH:9][C:5]=1[C:6]([OH:8])=[O:7].[CH3:15][C:16]([CH3:23])([CH3:22])[C:17](=O)[CH2:18][C:19]#[N:20].Cl.[OH-].[Na+]>C(O)C>[NH2:20][C:19]1[N:13]([C:11]2[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([O:3][CH3:2])[CH:12]=2)[N:14]=[C:17]([C:16]([CH3:23])([CH3:22])[CH3:15])[CH:18]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 108871Pentanenitrile, 4,4-dimethyl-3-oxo-HCID 674515382-Methoxy-4-hydrazinylbenzoic acid hydrochloride

Product 1

HCID 712531664-(5-amino-3-tert-butyl-1H-pyrazol-1-yl)-2-methoxybenzoic acidYield 71.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A suspension of 2-methoxy-4-hydrazinylbenzoic acid hydrochloride (1.05 g, 90% purity, 4.34 mmol) and 4,4-dimethyl-3-oxopentanenitrile (664 mg, 5.31 mmol) in ethanol (20 mL) containing conc hydrochloric acid (12 M, 0.44 mL, 5.0 mmol) was heated at reflux for 28 hr and then cooled to RT. The reaction mixture was treated with aq NaOH (2.0 M, 8.6 mL, 17 mmol) and was maintained at RT for 20 hr and then concentrated to half its original volume in vacuo. Then residue was washed with DCM (2×15 mL) and the aq layer was acidified to pH 5 with conc hydrochloric acid (12 M, 1.0 mL) and re-extracted with DCM (5×30 mL). The combined organic extracts were washed with brine (10 mL) and then dried and evaporated in vacuo to afford 4-(5-amino-3-tert-butyl-1H-pyrazol-1-yl)-2-methoxybenzoic acid as a brown solid (900 mg, 61%); Rt 1.47 min (Method 2); m/z 290 (M+H)+, (ES+).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 28 hr
  3. temperaturewas maintained at RT for 20 hr
  4. concentrationconcentrated to half its original volume in vacuo
  5. washThen residue was washed with DCM (2×15 mL)
  6. extractionre-extracted with DCM (5×30 mL)
  7. washThe combined organic extracts were washed with brine (10 mL)
  8. customdried
  9. customevaporated in vacuo

Sources & evidence

ORD record
ord-f9b02e844ad645a6bc07d6ae5f5d2f05
Source dataset
uspto-grants-2015_05
Patent number
US09024041B2

Reaction notes

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