Methyl iodide → Methyl 2',4',6'-trimethyl[1,1'-biphenyl]-4-carboxylate

HRID 915632Notes

Reaction equation

HRID 915632 reaction equation
I[C:2]1[C:7]([CH3:8])=[CH:6][C:5]([CH3:9])=[CH:4][C:3]=1[CH3:10].[C:11]([C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][CH:15]=1)([OH:13])=[O:12].P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH3:31]I>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CC([O-])=O.CC([O-])=O.[Pd+2].C(OCC)(=O)C>[CH3:31][O:13][C:11]([C:14]1[CH:19]=[CH:18][C:17]([C:2]2[C:7]([CH3:8])=[CH:6][C:5]([CH3:9])=[CH:4][C:3]=2[CH3:10])=[CH:16][CH:15]=1)=[O:12]

Participants

8

Reactant 4

HCID 6328Methyl iodideHCID 62657Potassium Phosphate, TribasicHCID 77647IodomesityleneHCID 3121834-Carboxyphenylboronic Acid

Product 1

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

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolvent

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, 1.2055 mmol), and potassium phosphate (2.557 g, 12.05 mmol). Purge the reaction vessel with argon and add anhydrous dimethylformamide (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 magnesium sulfate, 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 magnesium sulfate, filter, and evaporate to yield 0.023 g (16%) of the title compound. MS (m/e): 239.1 (M−).

Workup

  1. customPurge the reaction vessel with argon
  2. additionadd anhydrous dimethylformamide (20 mL) to the reaction mixture
  3. temperatureHeat
  4. customthe sealed reaction vessel to 120° C.
  5. temperatureCool
  6. customreaction mixture to room temperature
  7. stirringwith continued stirring until completion
  8. additionDilute
  9. filtrationfilter though a short plug of celite with additional ethyl acetate
  10. washWash the organics with water
  11. dry with materialdry over magnesium sulfate
  12. filtrationfilter
  13. customevaporate
  14. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-5a9de2fce09b49b8ba9b02d2c831580c
Source dataset
uspto-grants-2007_09
Patent number
US07265246B2

Reaction notes

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