Diethyl Ether → 3-Methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-5-carboxylic acid

HRID 2417685Notes

Reaction equation

HRID 2417685 reaction equation
[F:1][C:2]([F:6])([F:5])[CH2:3]O.[CH3:7][C:8]1[CH:12]=[C:11]([C:13]([O:15]CC)=[O:14])[NH:10][N:9]=1.CCOCC.[OH-].[NH4+]>C(O)C>[F:1][C:2]([F:6])([F:5])[CH2:3][N:10]1[C:11]([C:13]([OH:15])=[O:14])=[CH:12][C:8]([CH3:7])=[N:9]1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 64092,2,2-TrifluoroethanolHCID 14923Ammonium HydroxideHCID 178469061HCID 178469061, compound

Product 1

HCID 133384343-Methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-5-carboxylic acidYield 72%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 100 g (0.35 mol) of the trichloromethanesulfonate ester of 2,2,2-trifluoroethanol [J. Med. Chem. 16 1354 (1973)] and 55 g (0.35 mol) of ethyl 3-methylpyrazole-5-carboxylate is heated at 150°-155° C. for two hours. The cooled (70° C.) melt is poured with stirring into 400 ml of ether, 80 ml of conc. ammonium hydroxide, and 150 g ice. The ether layer is separated and distilled to give 48 g bp 100°-110°/11 mm. The ester is stirred under reflux two hours in 175 ml of ethanol and 40 ml of water containing 14 g of potassium hydroxide and evaporated in vacuo. The residue is dissolved in 60 ml of water and acidified with conc. HCl to give 32 g (72%) of 1-(2,2,2-trifluoroethyl)-3-methylpyrazole-5carboxylic acid, mp 135°-139° C.

Workup

  1. temperatureis heated at 150°-155° C. for two hours
  2. additionis poured
  3. customThe ether layer is separated
  4. distillationdistilled
  5. customto give 48 g bp 100°-110°/11 mm
  6. custom40 ml of water containing 14 g of potassium hydroxide and evaporated in vacuo
  7. dissolutionThe residue is dissolved in 60 ml of water

Sources & evidence

ORD record
ord-61e0a02c3f5444c285b367cf6c8b92f0
Source dataset
uspto-grants-1984_09
Patent number
US04469868

Reaction notes

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