Sodium Carbonate → Methyl 5-bromo-2'-fluoro-4'-methylbiphenyl-3-carboxylate

HRID 888360Notes

Reaction equation

HRID 888360 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10](I)[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[F:13][C:14]1[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][C:15]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Br:1][C:2]1[CH:3]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[CH:9]=[C:10]([C:15]2[CH:16]=[CH:17][C:18]([CH3:20])=[CH:19][C:14]=2[F:13])[CH:11]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2783132(2-Fluoro-4-methylphenyl)boronic acidHCID 21942573Methyl 3-bromo-5-iodobenzoate

Product 1

HCID 68499851Methyl 5-bromo-2'-fluoro-4'-methylbiphenyl-3-carboxylate

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

Methyl 3-bromo-5-iodo-benzoate (13 g) and 2-fluoro-4-methylphenylboronic acid (6 g) were dissolved in DMF (120 mL) at room temperature. The solution was then cooled down to 0° C. with ice bath. To this solution was added aq. sodium carbonate (6 g in 50 mL of water), Pd(dppf)Cl2 (3 g) and DMF (10 mL). After the addition, the reaction was warmed up slowly to room temperature. The reaction mixture was then stirred at room temperature for 4 hrs. Solvent was evaporated under reduced pressure. The residue was re-dissolved in EtOAc (200 mL) washed with HCl (1M) 3×200 mL), sat. NaHCO3 (3×100 mL), brine (3×100 mL) and water (3×100 mL). The organic layer was separated and concentrated. The crude product was then purified with column chromatography (silica gel, eluted with EtOAc/Hexane, 0 to 1%) to give pure compound. Note a second column can be done to further remove unwanted bis cross coupled by-product.

Workup

  1. additionAfter the addition
  2. temperaturethe reaction was warmed up slowly to room temperature
  3. customSolvent was evaporated under reduced pressure
  4. dissolutionThe residue was re-dissolved in EtOAc (200 mL)
  5. washwashed with HCl (1M) 3×200 mL), sat. NaHCO3 (3×100 mL), brine (3×100 mL) and water (3×100 mL)
  6. customThe organic layer was separated
  7. concentrationconcentrated
  8. customThe crude product was then purified with column chromatography (silica gel, eluted with EtOAc/Hexane, 0 to 1%)
  9. customto give pure compound

Sources & evidence

ORD record
ord-077fa0bc08784145a10ba6a28972de5b
Source dataset
uspto-grants-2012_08
Patent number
US08247401B2

Reaction notes

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