Lithium hydroxide, monohydrate → 1-tert-Butyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid

HRID 1930458Notes

Reaction equation

HRID 1930458 reaction equation
C(O)C.O.O1CCOCC1.[C:11]([N:15]1[C:19]([C:20]([F:23])([F:22])[F:21])=[C:18]([C:24]([O:26]CC)=[O:25])[CH:17]=[N:16]1)([CH3:14])([CH3:13])[CH3:12].O.[OH-].[Li+]>O.Cl>[C:11]([N:15]1[C:19]([C:20]([F:22])([F:23])[F:21])=[C:18]([C:24]([OH:26])=[O:25])[CH:17]=[N:16]1)([CH3:14])([CH3:12])[CH3:13]

Participants

6

Reactant 3

HCID 168937Lithium hydroxide, monohydrateHCID 2782985Ethyl 1-(tert-butyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylateHCID 69104347Dioxane ethanol water

Product 1

HCID 14820391-tert-Butyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acidYield 96.3%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 962WaterSolvent

Conditions

Temperature
40 °C

Procedure

In a solution of ethanol:water:dioxane (1:1:1, 9 mL) was placed ethyl 1-tert-butyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (750 mg, 2.84 mmol) and lithium hydroxide hydrate (357 mg, 8.51 mmol). The mixture was stirred at 40° C. for 3 hrs and then at RT overnight. The mixture was diluted with water (25 mL) and 1N HCl (10 mL) and extracted with ethyl acetate (2×25 mL). The combined organic phases were washed with brine (20 mL), dried (Na2SO4) and evaporated at reduced pressure to afford 1-tert-butyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid (646 mg, 94% yield) as a solid. 1H NMR (300 MHz, DMSO-d6) δ 1.63 (s, 9H), 7.92 (s, 1H); MS (ESI) m/z: 259.0 (M+Na+).

Workup

  1. customat RT
  2. customovernight
  3. extractionextracted with ethyl acetate (2×25 mL)
  4. washThe combined organic phases were washed with brine (20 mL)
  5. dry with materialdried (Na2SO4)
  6. customevaporated at reduced pressure

Sources & evidence

ORD record
ord-e92950f9ccee4d04b6f1491e890468d4
Source dataset
uspto-grants-2012_05
Patent number
US08188113B2

Reaction notes

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