Hydrochloric Acid → HCID 58763936, compound

HRID 859195Notes

Reaction equation

HRID 859195 reaction equation
[Li].C([O:4][C:5](=[O:18])[C:6](O)=[CH:7][C:8]([C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=1)=O)C.Cl.[Cl:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[NH:27][NH2:28].[OH-].[K+].Cl>C(O)C>[Cl:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[N:27]1[C:8]([C:10]2[CH:11]=[CH:12][C:13]([Cl:16])=[CH:14][CH:15]=2)=[CH:7][C:6]([C:5]([OH:4])=[O:18])=[N:28]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14797Potassium Hydroxide2×HCID 4432872-Chlorophenylhydrazine hydrochlorideHCID 178473082HCID 178473082, compound

Product 1

HCID 58763936HCID 58763936, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
0 °C

Procedure

4-(4-Chlorophenyl)-2-hydroxy-4-oxo-but-2-enoic acid ethyl ester lithium salt I-6a (30.26 g, 116 mmoles) was suspended in 242 ml of ethanol. 2-Chlorophenylhydrazine hydrochloride (20.88 g, 116 mmoles) was added portionwise as a solid over 45 minutes while maintaining an internal temperature between 30–40° C. Note: Reaction mixture goes from a yellow suspension to a dark orange suspension. Reaction stirred for 3 hours while maintaining internal temperature between 25–35° C. An aqueous potassium hydroxide solution (148 ml of 1.8 M solution, 266 mmoles) was added over 20 minutes while maintaining an internal temperature between 20–30° C. The reaction mixture was held for 2.5 hours. Note: Within 30 minutes of potassium hydroxide solution addition, reaction turned almost clear, very dark rust orange in color. Aqueous hydrochloric acid (85 ml of 3.9 M solution, 331 mmoles) was added over 15 minutes while maintaining reaction temperature between 20–30° C. Note: Product precipitated during hydrochloric acid addition. The precipitated product was granulated for 16 hours at room temperature. The crude product was isolated by filtration and the filtercake was washed with 150 ml of water. Note: Filtercake was a yellowish orange solid. After air-drying for 30 minutes, the filtercake was suspended in 480 ml of methanol. This suspension was heated to reflux to give a clear dark orange solution (all solids in solution within 1 hour of reaching reflux) that was held at reflux for 8 hours. The solution was cooled over 4 hours to room temperature, during which time product had precipitated from solution. The reaction mixture was held at room temperature for 10 hours, followed by cooling to 0° C., and stirring for 1.5 hours. Collection of the precipitate by filtration, washing the resulting filtercake with 150 ml of ice-chilled methanol, and drying at 60° C. and 1 mm for 3 hours afforded 1-(2-chlorophenyl)-5-(4-chlorophenyl)-1H-pyrazole-3-carboxylic acid I-6b (29.28 g, 76%) as an off-white solid.

Workup

  1. temperaturewhile maintaining an internal temperature between 30–40° C
  2. customReaction mixture
  3. customReaction
  4. temperaturewhile maintaining internal temperature between 25–35° C
  5. temperaturewhile maintaining an internal temperature between 20–30° C
  6. waitThe reaction mixture was held for 2.5 hours
  7. temperaturewhile maintaining
  8. customreaction temperature between 20–30° C
  9. customProduct precipitated during hydrochloric acid addition
  10. waitThe precipitated product was granulated for 16 hours at room temperature
  11. customThe crude product was isolated by filtration
  12. washthe filtercake was washed with 150 ml of water
  13. customAfter air-drying for 30 minutes
  14. temperatureThis suspension was heated
  15. temperatureto reflux
  16. customto give a clear dark orange solution (all solids in solution within 1 hour
  17. temperatureof reaching reflux) that
  18. temperatureat reflux for 8 hours
  19. temperatureThe solution was cooled over 4 hours to room temperature, during which time product
  20. customhad precipitated from solution
  21. waitThe reaction mixture was held at room temperature for 10 hours
  22. stirringstirring for 1.5 hours
  23. customCollection of the precipitate
  24. filtrationby filtration
  25. washwashing the resulting filtercake with 150 ml of ice-
  26. temperaturechilled methanol
  27. customdrying at 60° C.

Sources & evidence

ORD record
ord-a75b4bf1045640b7b28a42c5b9eb7c46
Source dataset
uspto-grants-2006_12
Patent number
US07151097B2

Reaction notes

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