Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphane → 4-[(4-{[tert-Butyl(dimethyl)silyl]oxy}phenyl)amino]-1-methyl-1H-pyrrole-2-carbonitrile

HRID 518929Notes

Reaction equation

HRID 518929 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]#[N:9])[N:5]([CH3:7])[CH:6]=1.[Si:10]([O:17][C:18]1[CH:24]=[CH:23][C:21]([NH2:22])=[CH:20][CH:19]=1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Si:10]([O:17][C:18]1[CH:24]=[CH:23][C:21]([NH:22][C:2]2[CH:3]=[C:4]([C:8]#[N:9])[N:5]([CH3:7])[CH:6]=2)=[CH:20][CH:19]=1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]

Participants

6

Reactant 3

HCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 117155534-((Tert-butyldimethylsilyl)oxy)anilineHCID 566989224-Bromo-1-methyl-1H-pyrrole-2-carbonitrile

Product 1

HCID 1317333114-[(4-{[tert-Butyl(dimethyl)silyl]oxy}phenyl)amino]-1-methyl-1H-pyrrole-2-carbonitrile

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

Nitrogen is bubbled through a solution of 4-bromo-1-methyl-1H-pyrrole-2-carbonitrile (2.82 g, 15.2 mmol) and 4-[(tert-butyldimethylsilyl)oxy]aniline (4.08 g, 18.3 mmol) in toluene (55 mL) for 5 minutes. Sodium tert-butylate (2.92 g, 30.4 mmol), tris(dibenzylideneacetone)dipalladium(0) (556 mg, 0.6 mmol) and 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (255 mg, 0.6 mmol) are then added to the reaction mixture. The mixture is stirred for 1 hour at 80° C. under nitrogen. The suspension is then cooled to ambient temperature and filtered over Celite. The Celite cake is then rinsed with ethyl acetate. The filtrate is washed with water and then with brine. The organic phase is dried over magnesium sulphate, filtered and concentrated in vacuo. The product is purified twice by chromatography over silica gel (AcOEt/heptane gradient), and then by trituration in heptane to obtain the expected product in the form of a solid.

Workup

  1. temperatureThe suspension is then cooled to ambient temperature
  2. filtrationfiltered over Celite
  3. washThe Celite cake is then rinsed with ethyl acetate
  4. washThe filtrate is washed with water
  5. dry with materialThe organic phase is dried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe product is purified twice by chromatography over silica gel (AcOEt/heptane gradient)

Sources & evidence

ORD record
ord-a1e0804e651042559dadf6df3f364ef6
Source dataset
uspto-grants-2015_08
Patent number
US09115159B2

Reaction notes

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