Sodium Carbonate → 4'-Chloro-2'-methyl[1,1'-biphenyl]-3-carboxylic acid

HRID 2375737Notes

Reaction equation

HRID 2375737 reaction equation
I[C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6].[Cl:11][C:12]1[CH:17]=[CH:16][C:15](B(O)O)=[C:14]([CH3:21])[CH:13]=1.C(=O)([O-])[O-].[Na+].[Na+]>[Pd].CC(O)C.O>[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([C:2]2[CH:10]=[CH:9][CH:8]=[C:4]([C:5]([OH:7])=[O:6])[CH:3]=2)=[C:14]([CH3:21])[CH:13]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 120603-Iodobenzoic acidHCID 5017600(4-Chloro-2-methylphenyl)boronic acid

Product 1

HCID 462383924'-Chloro-2'-methyl[1,1'-biphenyl]-3-carboxylic acid

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 21889133Propan-2-ol--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 3-iodobenzoic acid (11.9 g, 48 mmol), 4-chloro-2-methylphenylboronic acid (9.8 g, 57.7 mmol) and sodium carbonate (6.1 g, 57.7 mmol) under nitrogen atmosphere, was added i-PrOH-water (1/1, 180 mL) followed by 10% Pd—C (2 g, 19.2 mmol) with caution. The reaction mixture was heated at 80° C. under nitrogen overnight. The catalyst was removed by filtration, and the filtered catalyst was washed with EtOH (60 mL). Most of organic solvent was removed under reduced pressure. The resulting aqueous residue was treated with 2N HCl (aq) to bring the pH <2. The resulting mixture was extracted with EtOAc (2×100 mL). The combined organic extracts were washed with water and saturated brine, dried over Na2SO4, filtered and concentrated under reduced pressure. Compound 9.7 was obtained as white solid (12 g), which was used directly in the next step. MS ESI (neg.) m/e: 245 (M−H).

Workup

  1. customThe catalyst was removed by filtration
  2. washthe filtered catalyst was washed with EtOH (60 mL)
  3. customMost of organic solvent was removed under reduced pressure
  4. additionThe resulting aqueous residue was treated with 2N HCl (aq)
  5. extractionThe resulting mixture was extracted with EtOAc (2×100 mL)
  6. washThe combined organic extracts were washed with water and saturated brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-827ffb44a3534db188100792d3e5677c
Source dataset
uspto-grants-2008_12
Patent number
US07465804B2

Reaction notes

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