Potassium Carbonate → Methyl 2-hydroxy-2'-methyl-[1,1'-biphenyl]-4-carboxylate

HRID 1630992Notes

Reaction equation

HRID 1630992 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[OH:12].[C:13]1([CH3:22])[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>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:12][C:3]1[CH:4]=[C:5]([C:6]([O:8][CH3:9])=[O:7])[CH:10]=[CH:11][C:2]=1[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[CH3:22]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27332672-Methylphenyl boronic acidHCID 6425184Methyl 4-Bromo-3-hydroxybenzoate

Product 1

HCID 58554208Methyl 2-hydroxy-2'-methyl-[1,1'-biphenyl]-4-carboxylateYield 77%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of methyl 4-bromo-3-hydroxybenzoate (Combi-Blocks CA-4189, 25 g, 108 mmol), o-tolylboronic acid (22 g, 162 mmol), anhydrous potassium carbonate (44 g, 324 mmol) and Pd(PPh3)4 (6.25 g, 5.4 mmol) was prepared in a mixture of toluene (500 mL) and water (100 mL), and then degassed with N2. The reaction mixture was heated at 110° C. for 12 hours. The reaction mixture was cooled at RT, filtered through a Celite pad and washed with a 10% aqueous solution of NaHCO3, water and brine. The organic layer was dried (Na2SO4) and concentrated under vacuum. The residue was purified by chromatography (silica, pet ether/EtOAc) to afford of the title compound as a pale yellow solid (20 g, 77%). 1H NMR (DMSO-d6, 400 MHz) δ 9.85 (1H, s), 7.52 (1H, s), 7.45 (1H, d), 7.20-7.25, (3H, m), 7.15 (1H, d), 7.10 (1H, d), 3.84 (3H, s), 2.09 (3H, s).

Workup

  1. customdegassed with N2
  2. temperatureThe reaction mixture was cooled at RT
  3. filtrationfiltered through a Celite pad
  4. washwashed with a 10% aqueous solution of NaHCO3, water and brine
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by chromatography (silica, pet ether/EtOAc)

Sources & evidence

ORD record
ord-0e50e9758bc04fc589e1616ee5aabbf6
Source dataset
uspto-grants-2014_07
Patent number
US08791142B2

Reaction notes

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