Phthalonitrile → HCID 59596296, compound

HRID 2264725Notes

Reaction equation

HRID 2264725 reaction equation
Br[C:2]1[CH:15]=[CH:14][C:5]([O:6][Si:7]([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8])=[CH:4][CH:3]=1.C([Li])CCC.Br[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([Br:28])[CH:23]=1.[C:29]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[C:37]#[N:38])#[N:30].[Cl-].[NH4+]>O1CCCC1>[Br:28][C:24]1[CH:23]=[C:22]([C:29]2([C:2]3[CH:15]=[CH:14][C:5]([O:6][Si:7]([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8])=[CH:4][CH:3]=3)[C:31]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[C:37]([NH2:38])=[N:30]2)[CH:27]=[CH:26][CH:25]=1

Participants

7

Reactant 5

HCID 7042PhthalonitrileHCID 79271,3-DibromobenzeneHCID 25517Ammonium ChlorideHCID 4227167(4-Bromophenoxy)(tert-butyl)dimethylsilaneHCID 178418339Butyllithium2×

Product 1

HCID 59596296HCID 59596296, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a −78° C. cooled solution of (4-bromo-phenoxy)-tert-butyl-dimethyl-silane (3.82 mL, 15.61 mmol) in tetrahydrofuran (50 mL) was added 2.5 M n-butyllithium in hexanes (6.2 mL, 15.61 mmol) and the anion stirred 20 minutes. At the same time in a separate round bottom flask containing 1,3-dibromobenzene (2.83 mL, 23.41 mmol) and tetrahydrofuran (50 mL) cooled in a −78° C. bath was added 2.5 M n-butyllithium in hexanes (9.37 mL, 23.41 mmol) and the anion stirred 20 minutes. The first anion was cannulated into a −78° C. solution of 1,2-dicyanobenzene (2.00 g, 15.61 mmol) in tetrahydrofuran (20 mL) and this mixture stirred 10 minutes. The second anion was cannulated into the reaction and the mixture stirred 45 minutes. The reaction was poured into saturated ammonium chloride (100 mL) and extracted twice with ethyl acetate. The combined organic layers were washed with aqueous saturated sodium chloride, dried over magnesium sulfate and removed of solvent under reduced pressure to give an amber foam. The crude material was placed on a 180 g silica gel column and eluted with a gradient of dichloromethane to dichloromethane/methanol (9:1) over 30 minutes at 40 mL/min and the combined purified fractions were removed of solvent under reduced pressure to give the titled compound as a off white solid (1.64 g, 21%). 1H NMR (300 MHz, DMSO-d6) δ 7.69 (d, J=7.4 Hz, 1 H), 7.60-7.47 (m, 3 H), 7.42 (s, 2 H), 7.28 (d, J=7.5 Hz, 2 H), 7.14 (d, J=8.6 Hz, 2 H), 6.76 (d, J=8.6 Hz, 2 H), 0.92 (s, 9 H), 0.16 (s, 6 H); MS (APCI+) m/z 493 [M+1]+; tR=2.79 min.

Workup

  1. stirringthe anion stirred 20 minutes
  2. customwas cannulated into a −78° C.
  3. stirringthis mixture stirred 10 minutes
  4. customThe second anion was cannulated into the reaction
  5. stirringthe mixture stirred 45 minutes
  6. extractionextracted twice with ethyl acetate
  7. washThe combined organic layers were washed with aqueous saturated sodium chloride
  8. dry with materialdried over magnesium sulfate
  9. customremoved of solvent under reduced pressure
  10. customto give an amber foam
  11. washeluted with a gradient of dichloromethane to dichloromethane/methanol (9:1) over 30 minutes at 40 mL/min
  12. customthe combined purified fractions
  13. customwere removed of solvent under reduced pressure

Sources & evidence

ORD record
ord-847312e5336a4cd0ae6507978563e5fa
Source dataset
uspto-grants-2010_12
Patent number
US07855213B2

Reaction notes

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