Hydrochloric Acid → 1,4-dimethyl-3-(pentafluoroethyl)-1H-pyrazole-5-carboxylic acid

HRID 1843074Notes

Reaction equation

HRID 1843074 reaction equation
N([O:3][C:4](C)(C)C)=O.[Cu]C#N.[CH3:11][N:12]1[C:16](N)=[C:15]([CH3:18])[C:14]([C:19]([F:25])([F:24])[C:20]([F:23])([F:22])[F:21])=[N:13]1.[OH-:26].[K+].Cl>C(#N)C.O>[CH3:11][N:12]1[C:16]([C:4]([OH:3])=[O:26])=[C:15]([CH3:18])[C:14]([C:19]([F:25])([F:24])[C:20]([F:23])([F:22])[F:21])=[N:13]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 10906Tert-Butyl nitriteHCID 14797Potassium HydroxideHCID 585425741,4-dimethyl-3-(pentafluoroethyl)-1H-pyrazole-5-amineHCID 178418546HCID 178418546, compound

Product 1

HCID 585424991,4-dimethyl-3-(pentafluoroethyl)-1H-pyrazole-5-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
65 °C

Procedure

8.66 g (85.1 mmol) of tert-butyl nitrite and 6.0 g (67.4 mmol) of copper(I) cyanide are suspended in 360 ml of acetonitrile and heated to 65° C. A solution of 13.0 g (57.2 mmol) of 1,4-dimethyl-3-(pentafluoroethyl)-1H-pyrazole-5-amine in 20 ml of acetonitrile is then slowly added. The reaction mixture is further stirred for 24 hours at 65° C. The reaction mixture is then filtered over Celite. The filtrate is concentrated by evaporation under reduced pressure on a rotary evaporator. The residue is taken up in water and acidified with conc. hydrochloric acid. The aqueous phase is extracted several times with dichloromethane. The combined organic phases are concentrated by evaporation under reduced pressure on a rotary evaporator and the residue is purified by column chromatography on silica gel (hexane:ethyl acetate=5:1). The resulting product (2.3 g, 9.7 mmol) is heated under reflux with 3.44 g (63 mmol) of potassium hydroxide in 20 ml of water. After 3 h the reaction solution is cooled to 0° C. and adjusted to pH 6 with dilute hydrochloric acid. The resulting solid is filtered and dried. This gives 0.3 g of 1,4-dimethyl-3-(pentafluoroethyl)-1H-pyrazole-5-carboxylic acid (2%) as a white solid.

Workup

  1. filtrationThe reaction mixture is then filtered over Celite
  2. concentrationThe filtrate is concentrated by evaporation under reduced pressure on a rotary evaporator
  3. extractionThe aqueous phase is extracted several times with dichloromethane
  4. concentrationThe combined organic phases are concentrated by evaporation under reduced pressure on a rotary evaporator
  5. customthe residue is purified by column chromatography on silica gel (hexane:ethyl acetate=5:1)
  6. temperatureAfter 3 h the reaction solution is cooled to 0° C.
  7. filtrationThe resulting solid is filtered
  8. customdried

Sources & evidence

ORD record
ord-5c7a5074b6d74f629808fc6d9b2b54b4
Source dataset
uspto-grants-2015_02
Patent number
US08946234B2

Reaction notes

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