Lithium Hydroxide → 4-(2,4,6-Trimethylphenyl)benzoic acid

HRID 2224723Notes

Reaction equation

HRID 2224723 reaction equation
C[O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:16]([CH3:17])=[CH:15][C:14]([CH3:18])=[CH:13][C:12]=2[CH3:19])=[CH:7][CH:6]=1)=[O:4].[Li+].[OH-]>O1CCOCC1.O>[CH3:19][C:12]1[CH:13]=[C:14]([CH3:18])[CH:15]=[C:16]([CH3:17])[C:11]=1[C:8]1[CH:9]=[CH:10][C:5]([C:3]([OH:4])=[O:2])=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 13143477Methyl 2',4',6'-trimethyl[1,1'-biphenyl]-4-carboxylate

Product 1

HCID 227304674-(2,4,6-Trimethylphenyl)benzoic acidYield 16%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

Combine 1-iodo-2,4,6-trimethylbenzene (2.966 g, 12.05 mmol), 4-carboxyphenylboronic acid (1.0 g, 6.026 mmol), Pd(OAc)2 (0.0067 g, 0.005 mmol), tetrabutylammonium bromide (0.388 g, 1.206 mmol), and potassium phosphate (2.557 g, 12.05 mmol). Purge the reaction vessel with argon and add anhydrous DMF (20 mL) to the reaction mixture. Heat the sealed reaction vessel to 120° C. with stirring until completion as determined by TLC. Cool reaction mixture to room temperature. Add methyl iodide (1.0 mL, 36.63 mmol) to reaction mixture with continued stirring until completion. Dilute the reaction with ethyl acetate and filter though a short plug of celite with additional ethyl acetate. Wash the organics with water, dry over MgSO4, filter and evaporate. Purification by flash column chromatography yields 2′,4′,6′-trimethylbiphenyl-4-carboxylic acid methyl ester as a yellow solid. Dissolve the purified ester in dioxane (45 mL) and water (5 mL) containing 5 eq of LiOH with stirring at 60° C. Upon completion, evaporate the solvent, acidify the reaction mixture with hydrochloric acid, and extract with ethyl acetate. Dry the organics over MgSO4, filter, and evaporate to yield 0.023 g (16%) of the title compound. MS (ES): m/z 239.1 (M−H).

Workup

  1. customUpon completion, evaporate the solvent
  2. extractionextract with ethyl acetate
  3. dry with materialDry the organics over MgSO4
  4. filtrationfilter
  5. customevaporate

Sources & evidence

ORD record
ord-2df79fa897444821bb3c8ab8f81489f5
Source dataset
uspto-grants-2008_05
Patent number
US07378447B2

Reaction notes

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