Potassium Carbonate → Methyl 2'-methoxy-2-methylbiphenyl-4-carboxylate

HRID 336240Notes

Reaction equation

HRID 336240 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[CH3:12].[CH3:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=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>[CH3:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[CH3:12]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27339582-Methoxyphenylboronic acidHCID 3294148Methyl 4-bromo-3-methylbenzoate

Product 1

HCID 67528780Methyl 2'-methoxy-2-methylbiphenyl-4-carboxylateYield 80%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A suspension of methyl 4-bromo-3-methylbenzoate (4.9 g; 21.4 mmol; 1 eq.), 2-methoxyphenylboronic acid (Aldrich 44, 523-1; 3.6 g; 23.5 mmol; 1.1 eq.), potassium carbonate (14.8 g; 107 mmol; 5 eq.) and Pd(PPh3)4 (2.47 g; 2.14 mmol; 0.1 eq.) in toluene (24.5 mL) and water (24.5 mL) was refluxed for 6 hours. The reaction mixture was cooled down to room temperature and filtered through a pad of CELITE which was further washed with toluene (500 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 (200 mL), water (200 mL) and brine (200 mL) then dried over magnesium sulfate and concentrated in vacuo. The crude was purified by column chromatography (c-hexane/ethyl acetate, 90/10) to afford the title compound (4.38 g, 80%) as a colorless oil. HPLC (Method A): Rt 4.85 min (purity 98.9%). LC/MS: 257.0 (M+H)+.

Workup

  1. temperaturewas refluxed for 6 hours
  2. filtrationfiltered through a pad of CELITE which
  3. washwas further washed with toluene (500 mL)
  4. concentrationThe filtrate was concentrated in vacuo
  5. washThe organic layer was washed with sat. aq. NaHCO3 (200 mL), water (200 mL) and brine (200 mL)
  6. dry with materialthen dried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe crude was purified by column chromatography (c-hexane/ethyl acetate, 90/10)

Sources & evidence

ORD record
ord-2b85fdc295054511b9a04848deb94616
Source dataset
uspto-grants-2014_11
Patent number
US08889668B2

Reaction notes

Loading…