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

HRID 1517750Notes

Reaction equation

HRID 1517750 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:21]=[C:20]([CH3:22])[CH:19]=[CH:18][C:17]=1B(O)O.C(O)(C)C.C(=O)([O-])[O-].[Na+].[Na+]>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.O.CCOC(C)=O>[C:1]([O:5][C:6]([C:7]1[C:8]([C:17]2[CH:18]=[CH:19][C:20]([CH3:22])=[CH:21][C:16]=2[F:15])=[CH:9][CH:10]=[CH:11][CH:12]=1)=[O:14])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 3776IsopropanolHCID 10340Sodium CarbonateHCID 2783132(2-Fluoro-4-methylphenyl)boronic acidHCID 3804415tert-Butyl 2-bromobenzoate

Product 1

HCID 592838992'-Fluoro-4'-methylbiphenyl-2-carboxylic acid t-butyl esterYield 96%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

Compound A (22.8 g, 88.6 mmol) and 2-fluoro-4-methylphenylboronic acid (15.0 g, 97.4 mmol) were suspended in isopropyl alcohol (75 mL, 980 mmol). A solution of sodium carbonate (16 g, 150 mmol) in water (75 mL, 4.2 mol) was added and the mixture was degassed under nitrogen. Tetrakis(triphenylphosphine)palladium(0) (1.0 g, 880 μmol) was then added and the mixture was stirred at 90° C. overnight. The mixture was cooled to room temperature, EtOAc (200 mL) and water (200 mL) were added, and the mixture was filtered. The liquor was extracted with EtOAc (2×100 mL), washed with saturated aqueous NaCl, dried over MgSO4, filtered and concentrated. The material was purified by flash chromatography (0-15% EtOAc in hexanes) to yield compound B as a colorless oil (14.9 g, 96% purity).

Workup

  1. customthe mixture was degassed under nitrogen
  2. temperatureThe mixture was cooled to room temperature
  3. filtrationthe mixture was filtered
  4. extractionThe liquor was extracted with EtOAc (2×100 mL)
  5. washwashed with saturated aqueous NaCl
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe material was purified by flash chromatography (0-15% EtOAc in hexanes)

Sources & evidence

ORD record
ord-cd416af58d444b3090c3fe717adf75e5
Source dataset
uspto-grants-2012_07
Patent number
US08232306B2

Reaction notes

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