Potassium Carbonate → 2-(Hydroxymethyl)-2'-methylbiphenyl-4-carboxylic acid

HRID 2410484Notes

Reaction equation

HRID 2410484 reaction equation
C([O:4][CH2:5][C:6]1[CH:7]=[C:8]([CH:13]=[CH:14][C:15]=1Br)[C:9]([O:11]C)=[O:10])(=O)C.[C:17]1([CH3:26])[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=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>[OH:4][CH2:5][C:6]1[CH:7]=[C:8]([C:9]([OH:11])=[O:10])[CH:13]=[CH:14][C:15]=1[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[CH3:26]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 27332672-Methylphenyl boronic acidHCID 22574808Methyl 3-(acetoxymethyl)-4-bromobenzoate

Product 1

HCID 594957342-(Hydroxymethyl)-2'-methylbiphenyl-4-carboxylic acidYield 87.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture of methyl 3-[(acetyloxy)methyl]-4-bromobenzoate (4.7 g, 16.4 mmol), o-tolylboronic acid (2.45 g, 18 mmol), potassium carbonate (11.3 g, 82 mmol) and Pd(PPh3)4 (1.89 g, 1.64 mmol) in toluene (23.5 mL) and water (23.5 mL) was refluxed for 2 hours. After cooling to RT, the reaction mixture was filtered through a pad of Celite which was further washed with toluene (50 mL). The filtrate was concentrated in vacuo. The residue taken up in EtOAc (250 mL) and washed with a saturated aqueous solution of NaHCO3, water and brine, dried over magnesium sulphate and concentrated under vacuum. The residue was taken up with EtOH (180 mL) and treated with a 5N aqueous solution of NaOH (12 mL, 60 mmol) at 60° C. for 1.5 hours. The reaction mixture was concentrated under vacuum. The residue was taken up in water (500 mL) and the aqueous layer was washed twice with EtOAc (2×200 mL). The aqueous layer was acidified with a concentrated aqueous solution of HCl until pH 2 and extracted with EtOAc (2×100 mL). The combined organic layer were dried (MgSO4) and concentrated under vacuum to afford the title compound as a yellow solid (3.46 g, 87%). HPLC (Method A) Rt 3.77 min (purity 96.1%).

Workup

  1. temperaturewas refluxed for 2 hours
  2. filtrationthe reaction mixture was filtered through a pad of Celite which
  3. washwas further washed with toluene (50 mL)
  4. concentrationThe filtrate was concentrated in vacuo
  5. washwashed with a saturated aqueous solution of NaHCO3, water and brine
  6. dry with materialdried over magnesium sulphate
  7. concentrationconcentrated under vacuum
  8. concentrationThe reaction mixture was concentrated under vacuum
  9. washthe aqueous layer was washed twice with EtOAc (2×200 mL)
  10. extractionextracted with EtOAc (2×100 mL)
  11. dry with materialThe combined organic layer were dried (MgSO4)
  12. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-2769a6c89a634f4eae9cd838b8addf16
Source dataset
uspto-grants-2014_08
Patent number
US08815919B2

Reaction notes

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