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

HRID 630801Notes

Reaction equation

HRID 630801 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+].Cl[C:22]([O:24][CH2:25][C:26]([Cl:29])([Cl:28])[Cl:27])=[O:23]>CCOC(C)=O>[Cl:27][C:26]([Cl:29])([Cl:28])[CH2:25][O:24][C:22](=[O:23])[NH: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

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 870632,2,2-Trichloroethyl chloroformate2×HCID 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 79.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of Intermediate 71a (2.28 g, 9.49 mmol) in EtOAc (25 mL) and aqueous NaOH (1M, 23.7 mL, 23.7 mmol) was added 2,2,2-trichloroethyl chloroformate (1.57 mL, 11.4 mmol) dropwise over 2 min. A precipitate formed which redissolved after 15 min, then the orange solution was stirred at RT for 90 min. 2,2,2-Trichloroethyl chloroformate (0.391 mL, 2.85 mmol) was added and the orange mixture stirred at RT for 16 h. The layers were separated and the aqueous extracted with EtOAc (25 mL). The combined organics were washed with brine (25 mL), dried (Na2SO4), filtered and concentrated in vacuo to leave an orange-red oil. Recrystallisation from cyclohexane gave an off-white solid (3.12 g, 79%). LCMS (Method 3): Rt 4.46 min, m/z 415, 417 [MH+].

Workup

  1. customA precipitate formed which
  2. dissolutionredissolved after 15 min
  3. stirringthe orange mixture stirred at RT for 16 h
  4. customThe layers were separated
  5. extractionthe aqueous extracted with EtOAc (25 mL)
  6. washThe combined organics were washed with brine (25 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto leave an orange-red oil
  11. customRecrystallisation from cyclohexane

Sources & evidence

ORD record
ord-93321d7065cd442995aeb4db1887140a
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Reaction notes

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