Potassium Phosphate, Tribasic → Methyl 3-ethoxy-4'-fluorobiphenyl-4-carboxylate

HRID 530983Notes

Reaction equation

HRID 530983 reaction equation
[OH:1][C:2]1[CH:11]=[C:10](I)[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].P([O-])([O-])([O-])=O.[K+].[K+].[K+].[F:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1.[CH:31]1(P(C2CCCCC2)C2CCCCC2)CCCC[CH2:32]1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1>[CH2:31]([O:1][C:2]1[CH:11]=[C:10]([C:25]2[CH:26]=[CH:27][C:22]([F:21])=[CH:23][CH:24]=2)[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5])[CH3:32]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2856454-Fluorophenylboronic acidHCID 11380407Methyl 4-iodosalicylate

Product 1

HCID 117992167Methyl 3-ethoxy-4'-fluorobiphenyl-4-carboxylate

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

Palladium acetate (0.484 g) was added to a mixture of methyl 2-hydroxy-4-iodobenzoate (6.00 g), tripotassium phosphate (13.7 g), (4-fluorophenyl)boronic acid (6.04 g), tricyclohexylphosphine (20% toluene solution, 7.66 mL), toluene (30 mL), and water (15 mL), and the resultant mixture was stirred at 90° C. for 1.5 hours in an argon atmosphere. The reaction mixture was allowed to cool to room temperature, and then, the organic layer was separated. The aqueous layer was subjected to extraction with ethyl acetate. Combined organic layers were washed with saturated saline, then dried over anhydrous magnesium sulfate, and then passed through a short silica gel (NH) column, and the solvent was distilled off under reduced pressure. Iodoethane (2.59 mL) was added to a DMF (50 mL) suspension of the obtained residue and potassium carbonate (4.47 g), and the mixture was stirred at 80° C. for 1 hour. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The obtained organic layer was washed with saturated saline and passed through a short silica gel (NH) column, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (5.92 g).

Workup

  1. customthe organic layer was separated
  2. extractionThe aqueous layer was subjected to extraction with ethyl acetate
  3. washCombined organic layers were washed with saturated saline
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. additionIodoethane (2.59 mL) was added to a DMF (50 mL) suspension of the obtained residue and potassium carbonate (4.47 g)
  7. additionWater was added to the reaction mixture
  8. extractionfollowed by extraction with ethyl acetate
  9. washThe obtained organic layer was washed with saturated saline
  10. distillationthe solvent was distilled off under reduced pressure
  11. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-3a1a583a9ec441aca4efd41ea8756e81
Source dataset
uspto-grants-2016_05
Patent number
US09353108B2

Reaction notes

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