Water → 3'-Fluoro-4'-methylbiphenyl-2-carboxylic acid t-butyl ester

HRID 475668Notes

Reaction equation

HRID 475668 reaction equation
[C:1]([O:5][C:6](=[O:14])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1Br)([CH3:4])([CH3:3])[CH3:2].[F:15][C:16]1[CH:17]=[C:18](B(O)O)[CH:19]=[CH:20][C:21]=1[CH3:22].C(O)(C)C.C(=O)([O-])[O-].[Na+].[Na+].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>[C:1]([O:5][C:6]([C:7]1[C:8]([C:18]2[CH:19]=[CH:20][C:21]([CH3:22])=[C:16]([F:15])[CH:17]=2)=[CH:9][CH:10]=[CH:11][CH:12]=1)=[O:14])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 962WaterHCID 3776IsopropanolHCID 10340Sodium CarbonateHCID 27826743-Fluoro-4-methylbenzeneboronic acidHCID 3804415tert-Butyl 2-bromobenzoate

Product 1

HCID 574839403'-Fluoro-4'-methylbiphenyl-2-carboxylic acid t-butyl esterYield 76.6%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
90 °C

Procedure

Compound A (80.0 g, 311 mmol) and 3-fluoro-4-methylphenylboronic acid (52.7 g, 342 mmol) were suspended in isopropyl alcohol (260 mL, 3.5 mol). A solution of sodium carbonate (56.1 g, 529 mmol) in water (260 mL, 15 mol) was added and the mixture was degassed under nitrogen. Tetrakis(triphenylphosphine)palladium(0) (3.6 g, 3.1 mmol) was then added and the mixture was stirred at 90° C. for 17 hours. The mixture was concentrated under reduced pressure and suspended in water (200 mL). The aqueous phase was extracted with EtOAc (600 mL) and separated. The organic phase was washed with saturated aqueous NaCl and concentrated under reduced pressure. The recovered oil was purified by silica gel chromatography (4-6% 5×120 g column) to yield compound B as a clear oil (68.2 g).

Workup

  1. customthe mixture was degassed under nitrogen
  2. concentrationThe mixture was concentrated under reduced pressure
  3. extractionThe aqueous phase was extracted with EtOAc (600 mL)
  4. customseparated
  5. washThe organic phase was washed with saturated aqueous NaCl
  6. concentrationconcentrated under reduced pressure
  7. customThe recovered oil was purified by silica gel chromatography (4-6% 5×120 g column)

Sources & evidence

ORD record
ord-42eba26a4feb4aff94b1503ef8fed07e
Source dataset
uspto-grants-2014_01
Patent number
US08637562B2

Reaction notes

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