Hydrochloric Acid → ethyl 5-chloro-1-(4-fluorophenyl)-1H-pyrazole-4-carboxylate

HRID 1744472Notes

Reaction equation

HRID 1744472 reaction equation
N[C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:14]([O:16][CH2:17][CH3:18])=[O:15].N([O-])=O.[Na+].[ClH:23]>[Cu]Cl>[Cl:23][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:14]([O:16][CH2:17][CH3:18])=[O:15]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 688689ethyl 5-amino-1-(4-fluorophenyl)-1H-pyrazole-4-carboxylateHCID 23668193Sodium Nitrite

Product 1

HCID 22228090ethyl 5-chloro-1-(4-fluorophenyl)-1H-pyrazole-4-carboxylate

Reagents, catalysts & solvents 1

HCID 62652Cuprous chlorideCatalyst

Procedure

Ethyl 5-amino-1-(4-fluorophenyl)pyrazole-4-carboxylate (5.4 g) was dissolved in 12N hydrochloric acid, and aqueous solution (10 ml) containing sodium nitrite (4.5 g) was added dropwise thereto under ice-cooling, which was followed by stirring for 2 h. An aqueous solution (10 ml) containing copper(I) chloride (10.7 g) was added and the mixture was stirred for 30 min. The mixture was warmed to room temperature and stirred further for 2 h. Solid was filtered off with Celite and ethyl acetate was added to the filtrate to separate the organic layer. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, after which the solvent was evaporated under reduced pressure. n-Hexane was added to the obtained residue to allow crystallization. The crystals were recrystallized from a mixed solvent of ethyl acetate-n-hexane to give ethyl 5-chloro-1-(4-fluorophenyl)pyrazole-4-carboxylate (3.5 g), melting point: 70–72° C.

Workup

  1. additionwas added dropwise
  2. temperatureunder ice-cooling
  3. additionwas added
  4. stirringthe mixture was stirred for 30 min
  5. stirringstirred further for 2 h
  6. filtrationSolid was filtered off with Celite and ethyl acetate
  7. additionwas added to the filtrate
  8. customto separate the organic layer
  9. washThe organic layer was washed with saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customafter which the solvent was evaporated under reduced pressure
  12. additionn-Hexane was added to the obtained residue
  13. customcrystallization
  14. customThe crystals were recrystallized from a mixed solvent of ethyl acetate-n-hexane

Sources & evidence

ORD record
ord-cb4307df30ed4f9d8cd366d2abd2dcad
Source dataset
uspto-grants-2006_03
Patent number
US07015218B1

Reaction notes

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