Potassium Carbonate → Methyl 2'-ethyl-2-(methoxymethyl)-[1,1'-biphenyl]-4-carboxylate

HRID 1630971Notes

Reaction equation

HRID 1630971 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[CH2:12][O:13][CH3:14].[CH2:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1B(O)O)[CH3:16].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>[CH2:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[CH2:12][O:13][CH3:14])[CH3:16]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 41008622-Ethylphenylboronic Acid (contains varying amounts of Anhydride)HCID 58554220Methyl 4-bromo-3-(methoxymethyl)benzoate2×

Product 1

HCID 58554174Methyl 2'-ethyl-2-(methoxymethyl)-[1,1'-biphenyl]-4-carboxylateYield 91.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of methyl 4-bromo-3-(methoxymethyl)benzoate (12.0 g, 46.3 mmol, Intermediate A1 step 2) in toluene (150 mL) and water (35 mL) was added 2-ethyl benzene boronic acid (9.0 g, 60.1 mmol) followed by potassium carbonate (19.0 g, 139 mmol) and Pd(PPh3)4 (2.7 g, 2.3 mmol). The resulting mixture was degassed with N2 for 10 min and heated at 100° C. for 12 hours. The reaction mixture was diluted with EtOAc. The organic layer was washed with a saturated aqueous solution of NaHCO3, water (2×) and brine, and then dried (Na2SO4). The solvents were removed under reduced pressure. The residue was purified by chromatography (silica, pet ether/EtOAc) to afford the title compound as a pale yellow oil (12.0 g, 83%). 1H NMR (CDCl3, 400 MHz) δ 8.25 (1H, s), 8.00 (1H, d), 7.35 (2H, m), 7.25 (2H, m), 7.08 (1H, d), 4.17 (2H, m), 3.94 (3H, s), 3.29 (3H, s), 2.43-2.28 (2H, m), 1.03 (3H, t).

Workup

  1. customThe resulting mixture was degassed with N2 for 10 min
  2. additionThe reaction mixture was diluted with EtOAc
  3. washThe organic layer was washed with a saturated aqueous solution of NaHCO3, water (2×) and brine
  4. dry with materialdried (Na2SO4)
  5. customThe solvents were removed under reduced pressure
  6. customThe residue was purified by chromatography (silica, pet ether/EtOAc)

Sources & evidence

ORD record
ord-ec4946b04789425d91eb20954ab396a5
Source dataset
uspto-grants-2014_07
Patent number
US08791142B2

Reaction notes

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