Sodium Hydroxide → 2,2,2-Trichloroethyl 3-tert-butyl-1-(4-cyanophenyl)-1H-pyrazol-5-ylcarbamate

HRID 220223Notes

Reaction equation

HRID 220223 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][CH:8]=2)[N:5]=[C:4]([C:15]([CH3:18])([CH3:17])[CH3:16])[CH:3]=1.[OH-].[Na+].[C:21](Cl)(=[O:28])[O:22][CH2:23][C:24]([Cl:27])([Cl:26])[Cl:25]>C(OCC)(=O)C>[C:15]([C:4]1[CH:3]=[C:2]([NH:1][C:21](=[O:28])[O:22][CH2:23][C:24]([Cl:27])([Cl:26])[Cl:25])[N:6]([C:7]2[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][CH:8]=2)[N:5]=1)([CH3:18])([CH3:17])[CH3:16]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 870632,2,2-Trichloroethyl chloroformateHCID 71470834-(5-Amino-3-tert-butyl-1H-pyrazol-1-yl)benzonitrile

Product 1

HCID 687825092,2,2-Trichloroethyl 3-tert-butyl-1-(4-cyanophenyl)-1H-pyrazol-5-ylcarbamateYield 30.9%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

4-(5-Amino-3-tert-butyl-1H-pyrazol-1-yl)benzonitrile (11.8 g, 49.1 mmol) was added to 70 mL of 3 N NaOH and 100 mL of ethyl acetate and the reaction mixture was cooled in an ice-bath. 2,2,2-Trichloroethyl carbonochloridate (9.34 mL, 68.7 mmol) was slowly added and the reaction was warmed to ambient temperature with stirring overnight. The ethyl acetate layer was washed with 3 N HCl and brine, and the organic layer was dried over MgSO4, filtered and concentrated to an oil. Hexane was added to this oil and the mixture was stirred rapidly until a solid formed. The solids were triturated in hexanes, filtered, and dissolved in minimal warm ethyl acetate. Hexanes were added to the ethyl acetate solution until a slight cloudiness was observed. Material was allowed to crystallize and the solids were collected by filtration to yield 6.3 g of the desired product as a white solid, MS M+1 (416).

Workup

  1. temperaturethe reaction mixture was cooled in an ice-bath
  2. washThe ethyl acetate layer was washed with 3 N HCl and brine
  3. dry with materialthe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated to an oil
  6. additionHexane was added to this oil
  7. stirringthe mixture was stirred rapidly until a solid
  8. customformed
  9. customThe solids were triturated in hexanes
  10. filtrationfiltered
  11. dissolutiondissolved
  12. temperaturein minimal warm ethyl acetate
  13. additionHexanes were added to the ethyl acetate solution until a slight cloudiness
  14. customto crystallize
  15. filtrationthe solids were collected by filtration

Sources & evidence

ORD record
ord-fb2ca754071e4f1b91311bdc2e95a752
Source dataset
uspto-grants-2012_06
Patent number
US08202899B2

Reaction notes

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