Potassium Carbonate → Methyl 4-(4-chlorophenoxy)-2-fluoro-5-(2-methoxypyridin-3-yl)benzoate

HRID 1620345Notes

Reaction equation

HRID 1620345 reaction equation
Br[C:2]1[C:3]([O:13][C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)=[CH:4][C:5]([F:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].C(=O)([O-])[O-].[K+].[K+].O.[CH3:28][O:29][C:30]1[C:35](B(O)O)=[CH:34][CH:33]=[CH:32][N:31]=1>O1CCOCC1.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>[Cl:20][C:17]1[CH:18]=[CH:19][C:14]([O:13][C:3]2[C:2]([C:35]3[C:30]([O:29][CH3:28])=[N:31][CH:32]=[CH:33][CH:34]=3)=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[C:5]([F:12])[CH:4]=2)=[CH:15][CH:16]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 441197962-Methoxypyridine-3-boronic acid hydrateHCID 66666677Methyl 5-bromo-4-(4-chlorophenoxy)-2-fluorobenzoate

Product 1

HCID 66667452Methyl 4-(4-chlorophenoxy)-2-fluoro-5-(2-methoxypyridin-3-yl)benzoateYield 179.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred solution of methyl 5-bromo-4-(4-chlorophenoxy)-2-fluorobenzoate (Preparation 32, 199 mg, 0.55 mmol) in dioxane (10 mL) and water (0.5 mL) was added potassium carbonate (158 mg, 1.14 mmol) and 2-methoxypyridin-3-ylboronic acid mono hydrate (147 mg, 0.86 mmol). The reaction was degassed three times followed by the addition of tetrakis(triphenylphosphine)palladium(0) (13.2 mg, 0.012 mmol). The reaction was degassed three times and heated at 50° C. overnight under a nitrogen atmosphere. The reaction was cooled to room temperature, concentrated in vacuo to afford a brown residue. The residue was partitioned between EtOAc (25 mL) and water (25 mL). The aqueous phase was extracted with EtOAc (2×25 mL). The combined organic extracts were washed with water (25 mL), brine (25 mL), dried over sodium sulfate, filtered and concentrated in vacuo to afford brown oil (383 mg). The oil was then purified by flash column chromatography using the Biotage System™ (50 g silica column, eluting with DCM). Fractions containing product were combined and concentrated in vacuo to afford the title compound as a grey oil (194 mg, 91%).

Workup

  1. customThe reaction was degassed three times
  2. customThe reaction was degassed three times
  3. temperatureThe reaction was cooled to room temperature
  4. concentrationconcentrated in vacuo
  5. customto afford a brown residue
  6. customThe residue was partitioned between EtOAc (25 mL) and water (25 mL)
  7. extractionThe aqueous phase was extracted with EtOAc (2×25 mL)
  8. washThe combined organic extracts were washed with water (25 mL), brine (25 mL)
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e1916f5a0b4941b3b759a40b9e7c5a14
Source dataset
uspto-grants-2014_07
Patent number
US08772343B2

Reaction notes

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