Toluene → HCID 66604642, compound

HRID 2410693Notes

Reaction equation

HRID 2410693 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][O:18][Si:19]([CH:26]([CH3:28])[CH3:27])([CH:23]([CH3:25])[CH3:24])[CH:20]([CH3:22])[CH3:21])[CH:12]=2)=[C:6]([CH:9]=1)[C:7]#[N:8].C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].[Cl:42][C:43]1[CH:44]=[C:45](B(O)O)[CH:46]=[CH:47][C:48]=1[Cl:49]>CO.O.CCOC(C)=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:42][C:43]1[CH:44]=[C:45]([C:2]2[CH:3]=[CH:4][C:5]([NH:10][C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][O:18][Si:19]([CH:20]([CH3:21])[CH3:22])([CH:26]([CH3:28])[CH3:27])[CH:23]([CH3:25])[CH3:24])[CH:12]=3)=[C:6]([C:7]#[N:8])[CH:9]=2)[CH:46]=[CH:47][C:48]=1[Cl:49]

Participants

9

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27343303,4-Dichlorobenzeneboronic acidHCID 66605360HCID 66605360, compound

Product 1

HCID 66604642HCID 66604642, compoundYield 54.2%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of crude 5-bromo-2-(3-((triisopropylsilyloxy)methyl)phenylamino)benzonitrile (3.9 g, 8.49 mmol), tetrakis(triphenylphosphine)palladium(0) (0.438 g, 0.379 mmol), toluene (60 mL), and 2 M aqueous sodium carbonate (9.63 mL, 19.27 mmol) under nitrogen were added a solution of 3,4-dichlorophenylboronic acid (2.203 g, 11.54 mmol) in MeOH (14 mL) at rt. The resulting reaction mixture was heated at reflux for 4 h. After cooling to room temperature, it was diluted with a mixture of water (150 mL) and EtOAc (250 mL) and the two phases were separated. The aqueous phase was extracted with ethyl acetate (2×100 mL), and the combined organic phases were washed with water (2×100 mL), 5% aqueous NH4OH solution (100 mL), and brine (100 mL). The organic phase was dried over Na2SO4 and the solvent removed. The crude material was purified by chromatography on silica gel, eluting with hexane containing 2%-5% EtOAc afforded 2.42 g of 3′,4′-dichloro-4-(3-((triisopropylsilyloxy)methyl)phenylamino)-biphenyl-3-carbonitrile. 1H NMR (CDCl3) δ ppm 7.65 (1H, d, J=1.83 Hz), 7.53-7.58 (2H, m), 7.39 (1H, dd, J=9.00, 2.29 Hz), 7.31 (1H, t, J=7.78 Hz), 7.22 (1H, s), 7.11 (1H, d, J=7.63 Hz), 7.07 (1H, d, J=8.85 Hz), 7.02 (2H, d, J=8.24 Hz), 6.35 (1H, s), 4.82 (2H, s), 1.13-1.22 (3H, m), 1.06-1.11 (18H, m).

Workup

  1. customThe resulting reaction mixture
  2. temperaturewas heated
  3. temperatureat reflux for 4 h
  4. customthe two phases were separated
  5. extractionThe aqueous phase was extracted with ethyl acetate (2×100 mL)
  6. washthe combined organic phases were washed with water (2×100 mL), 5% aqueous NH4OH solution (100 mL), and brine (100 mL)
  7. dry with materialThe organic phase was dried over Na2SO4
  8. customthe solvent removed
  9. customThe crude material was purified by chromatography on silica gel
  10. washeluting with hexane containing 2%-5% EtOAc

Sources & evidence

ORD record
ord-e77706ea88ee4a45bfdc5b1889acf253
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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