Potassium Carbonate → 3-Methoxy-4-(2-methylphenyl)benzoic acid

HRID 336242Notes

Reaction equation

HRID 336242 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8]C)=[O:7])=[CH:4][C:3]=1[O:12][CH3:13].[C:14]1([CH3:23])[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1B(O)O.C(=O)([O-])[O-].[K+].[K+].[OH-].[Na+]>C1(C)C=CC=CC=1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:13][O:12][C:3]1[CH:4]=[C:5]([C:6]([OH:8])=[O:7])[CH:10]=[CH:11][C:2]=1[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[CH3:23]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 27332672-Methylphenyl boronic acidHCID 14570117Methyl 4-bromo-3-methoxybenzoate

Product 1

HCID 180010763-Methoxy-4-(2-methylphenyl)benzoic acidYield 79%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A suspension of methyl 4-bromo-3-methoxybenzoate (Combi-blocks CA-4192; 2.5 g; 10.2 mmol; 1 eq.), o-tolylboronic acid (Aldrich 393606; 1.53 g; 11.2 mmol; 1.1 eq.), potassium carbonate (7.05 g; 51 mmol; 5 eq.) and Pd(PPh3)4 (1.18 g; 1.02 mmol; 0.1 eq.) in toluene (12.5 mL) and water (12.5 mL) was refluxed for 2 hours. The reaction mixture was cooled down to room temperature and filtered through a pad of CELITE which was further washed with toluene (200 mL). The filtrate was concentrated in vacuo and the residue taken up in Ethyl acetate (500 mL). The organic layer was washed with sat. aq. NaHCO3 (150 mL), water (150 mL) and brine (150 mL) then dried over magnesium sulfate and concentrated in vacuo. The residue (2.5 g; 9.75 mmol; 1 eq.) was taken up in EtOH (75 mL), sodium hydroxide (5M; 5.85 mL; 29.3 mmol; 3 eq.) was added and the reaction mixture was stirred at 60° C. for two hours. After concentration in vacuo, the residue was taken up in water (400 mL) and the aqueous phase was washed with Ethyl acetate then acidified to pH 2 with conc. HCl. The solution was concentrated to ca. 80 mL and the precipitate filtered off and dried to afford the title compound (1.95 g, 79%) as a beige solid.

Workup

  1. temperaturewas refluxed for 2 hours
  2. filtrationfiltered through a pad of CELITE which
  3. washwas further washed with toluene (200 mL)
  4. concentrationThe filtrate was concentrated in vacuo
  5. washThe organic layer was washed with sat. aq. NaHCO3 (150 mL), water (150 mL) and brine (150 mL)
  6. dry with materialthen dried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. concentrationAfter concentration in vacuo
  9. washthe aqueous phase was washed with Ethyl acetate
  10. concentrationThe solution was concentrated to ca. 80 mL
  11. filtrationthe precipitate filtered off
  12. customdried

Sources & evidence

ORD record
ord-570389d9186e44b7b72f5ab1a58ed3b9
Source dataset
uspto-grants-2014_11
Patent number
US08889668B2

Reaction notes

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