Toluene → HCID 66599429, compound

HRID 2410694Notes

Reaction equation

HRID 2410694 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:10])=[C:6]([CH:9]=1)[C:7]#[N:8].C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].[Cl:24][C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][C:30]=1[Cl:31]>CO.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:24][C:25]1[CH:26]=[C:27]([C:2]2[CH:3]=[CH:4][C:5]([F:10])=[C:6]([C:7]#[N:8])[CH:9]=2)[CH:28]=[CH:29][C:30]=1[Cl:31]

Participants

8

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27249005-Bromo-2-fluorobenzonitrileHCID 27343303,4-Dichlorobenzeneboronic acid

Product 1

HCID 66599429HCID 66599429, compoundYield 90.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of 5-bromo-2-fluorobenzonitrile (400 mg, 2.000 mmol) and (Ph3P)4Pd (116 mg, 0.100 mmol) were mixed in a microwave tube (20 mL) and flushed with nitrogen. Toluene (5 mL), 2 M aqueous sodium carbonate (2.270 mL, 4.54 mmol) and a solution of 3,4-dichlorophenylboronic acid (519 mg, 2.72 mmol) in MeOH (3 mL) were added. The mixture was heated in an oil bath at 105° C. for 4.5 h. After cooling to room temperature, the reaction was diluted with water (10 mL) and the two phases were separated. The aqueous phase was extracted with ethyl acetate (20 mL), and combined organic phases were washed with water (2×10 mL), 5% aqueous NH4OH (10 mL), and brine (10 mL). The organic phase was dried over Na2SO4 and the solvent was removed. The residue was chromatographed on silica gel eluting with hexane containing 0, 2, 3% ethyl acetate to afford 480 mg of product as a white solid which was about 76% pure by LC/MS. This was used as such in the next step.

Workup

  1. additionwere mixed in a microwave tube (20 mL)
  2. customflushed with nitrogen
  3. temperatureAfter cooling to room temperature
  4. customthe two phases were separated
  5. extractionThe aqueous phase was extracted with ethyl acetate (20 mL)
  6. washwere washed with water (2×10 mL), 5% aqueous NH4OH (10 mL), and brine (10 mL)
  7. dry with materialThe organic phase was dried over Na2SO4
  8. customthe solvent was removed
  9. customThe residue was chromatographed on silica gel eluting with hexane containing 0, 2, 3% ethyl acetate

Sources & evidence

ORD record
ord-7610e41db9ab436bbc478598075a08cf
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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