Hydrochloric Acid → 1-(4-Methoxybenzyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid

HRID 1890769Notes

Reaction equation

HRID 1890769 reaction equation
[Li+].[OH-].[CH3:3][O:4][C:5]1[CH:25]=[CH:24][C:8]([CH2:9][N:10]2[CH:14]=[C:13]([C:15]([O:17]CC)=[O:16])[C:12]([C:20]([F:23])([F:22])[F:21])=[N:11]2)=[CH:7][CH:6]=1.Cl>O.O1CCOCC1>[CH3:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([CH2:9][N:10]2[CH:14]=[C:13]([C:15]([OH:17])=[O:16])[C:12]([C:20]([F:21])([F:22])[F:23])=[N:11]2)=[CH:24][CH:25]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 58243468Ethyl 1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate

Product 1

HCID 582442211-(4-Methoxybenzyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acidYield 27.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Add a solution of LiOH (122 mg, 5.03 mmol) in H2O (3 mL) to a stirred solution of ethyl 1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate (550 mg, 1.68 mmol) in 1,4-dioxane (10 mL). Stir overnight at ambient temperature. Acidify to pH 5 with 1 N HCl and extract with CH2Cl2 and 2× with 20% iPrOH in CHCl3. Dry the combined organic layers with MgSO4, filter and concentrate under reduced pressure to obtain 140 mg of the title compound as a white solid. Acidify the aqueous layer to pH 2-3 with 1 N HCl, and extract twice with 20% iPrOH in CHCl3. Dry the combined organics over MgSO4, filter, and add the solution to the initially obtained 140 mg white solids. Concentrate to afford the title compound as a white solid (426 mg, 85%). ES/MS m/z 299.0 (M−1).

Workup

  1. extractionextract with CH2Cl2 and 2× with 20% iPrOH in CHCl3
  2. dry with materialDry the combined organic layers with MgSO4
  3. filtrationfilter
  4. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-cb274629f6b24b529264e879a8cd43b4
Source dataset
uspto-grants-2013_08
Patent number
US08507490B2

Reaction notes

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