Ethanol → ethyl 3-(5-amino-3-tert-butyl-1H-pyrazol-1-yl)benzoate

HRID 424133

Reaction equation

HRID 424133 reaction equation
S(=O)(=O)(O)O.[NH:6]([C:8]1[CH:9]=[C:10]([CH:14]=[CH:15][CH:16]=1)[C:11]([OH:13])=[O:12])[NH2:7].[CH3:17][C:18]([CH3:25])([CH3:24])[C:19](=O)[CH2:20][C:21]#[N:22].[CH3:26][CH2:27]O>>[NH2:22][C:21]1[N:6]([C:8]2[CH:9]=[C:10]([CH:14]=[CH:15][CH:16]=2)[C:11]([O:13][CH2:26][CH3:27])=[O:12])[N:7]=[C:19]([C:18]([CH3:25])([CH3:24])[CH3:17])[CH:20]=1

Participants

5

Reactant 4

HCID 702EthanolHCID 1118Sulfuric AcidHCID 108871Pentanenitrile, 4,4-dimethyl-3-oxo-HCID 27365213-Hydrazinobenzoic acid

Product 1

HCID 21867322ethyl 3-(5-amino-3-tert-butyl-1H-pyrazol-1-yl)benzoateYield 71%

Conditions

Temperature
90 °C

Procedure

Sulfuric acid (concentrated, 15.7 mL, 295.7 mmol) was carefully added drop-wise to cold EtOH (600 mL) with stirring. To this, 3-hydrazinobenzoic acid (45 g, 295.7 mmol) and 4,4-dimethyl-3-oxopentanenitrile (40.7 g, 325.3 mmol) were added and then the mixture was heated at 90° C. for 48 h. Most of the solvent was evaporated at reduced pressure, and the residual mixture was diluted with ethyl acetate. The resulting mixture was washed with ice cold 2M NaOH followed by brine, and dried (Na2SO4). The solution was filtered through a bed of silica gel, washing with more ethyl acetate. Evaporation of ethyl acetate and treatment of the residue with dichloromethane/hexanes gave the product as an off-white crystalline solid (61 g, 71%). MS m/z 288.2 (M+H)+; calcd. mass 287. Retention time (LC-MS): 2.99 min. 1H-NMR (DMSO-d6): δ 8.16 (m 1H); 7.88 (m, 2H); 7.60 (t, 1H); 5.40 (s, 1H); 5.32 (s, 2H); 4.36 (q, 2H); 1.34 (t, 3H); 1.21 (s, 9H).

Workup

  1. customMost of the solvent was evaporated at reduced pressure
  2. additionthe residual mixture was diluted with ethyl acetate
  3. washThe resulting mixture was washed with ice cold 2M NaOH
  4. dry with materialdried (Na2SO4)
  5. filtrationThe solution was filtered through a bed of silica gel
  6. washwashing with more ethyl acetate
  7. customEvaporation of ethyl acetate and treatment of the residue with dichloromethane/hexanes

Sources & evidence

ORD record
ord-f242747c6aa64093869d5d52559006b8
Source dataset
uspto-grants-2012_01
Patent number
US08101773B2

Linked notes

Loading…