Sodium Carbonate → Methyl 2-(3-methyl-4-fluorophenyl)-5-fluorobenzoate

HRID 1460364Notes

Reaction equation

HRID 1460364 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][C:3]=1[CH3:11].Br[C:13]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:14]=1[C:15]([O:17][CH3:18])=[O:16].C(=O)([O-])[O-].[Na+].[Na+].[OH-].[NH4+]>O.C(O)C.C1(C)C=CC=CC=1>[CH3:11][C:3]1[CH:4]=[C:5]([C:13]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:14]=2[C:15]([O:17][CH3:18])=[O:16])[CH:6]=[CH:7][C:2]=1[F:1]

Participants

8

Reactant 4

HCID 10340Sodium Carbonate2×HCID 14923Ammonium HydroxideHCID 138875Benzoic acid, 2-bromo-5-fluoro-, methyl esterHCID 2774580(4-Fluoro-3-methylphenyl)boronic acid

Product 1

HCID 15037296Methyl 2-(3-methyl-4-fluorophenyl)-5-fluorobenzoateYield 98.7%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture of 4-fluoro-3-methylphenylboronic acid (6.5 g, 42.5 mmol), methyl 2-bromo-5-fluorobenzoate (10.0 g, 42.9 mmol), tetrakis (triphenylphospine) palladium(0) (1.0 g, 0.87 mmol, 0.2 eq), toluene (100 mL), 2M aqueous sodium carbonate (50 mL) and ethanol (25 mL) was refluxed for 9 h. The reaction mixture was then poured into 50 mL each of concentrated ammonium hydroxide, 2M aqueous sodium carbonate, and water, the organic phase was separated, and the aqueous was extracted with ethyl acetate. The combined organics were washed with brine, dried over MgSO4, and concentrated to leave an oil which was chromatographed on silica gel using hexane to provide 11 g (98%) of the ester.

Workup

  1. temperaturewas refluxed for 9 h
  2. customthe organic phase was separated
  3. extractionthe aqueous was extracted with ethyl acetate
  4. washThe combined organics were washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customto leave an oil which
  8. customwas chromatographed on silica gel

Sources & evidence

ORD record
ord-d58dfe5feaa74d62a802ffa05488e10c
Source dataset
uspto-grants-1991_12
Patent number
US05070100

Reaction notes

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