Sodium Carbonate → 3-(4-((Tert-butyl(dimethyl)silyl)oxy)-2'-fluoro-5'-methoxybiphenyl-2-yl)-2,2-dimethylpropanenitrile

HRID 1049486Notes

Reaction equation

HRID 1049486 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][Si:9]([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10])=[CH:4][C:3]=1[CH2:16][C:17]([CH3:21])([CH3:20])[C:18]#[N:19].[F:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][C:24]=1B(O)O.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C(=O)([O-])[O-].[Na+].[Na+]>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:9]([O:8][C:5]1[CH:6]=[CH:7][C:2]([C:24]2[CH:25]=[C:26]([O:29][CH3:30])[CH:27]=[CH:28][C:23]=2[F:22])=[C:3]([CH2:16][C:17]([CH3:21])([CH3:20])[C:18]#[N:19])[CH:4]=1)([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 41572112-Fluoro-5-methoxyphenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 1317360143-(2-Bromo-5-((tert-butyl(dimethyl)silyl)oxy)phenyl)-2,2-dimethylpropanenitrile

Product 1

HCID 1317360153-(4-((Tert-butyl(dimethyl)silyl)oxy)-2'-fluoro-5'-methoxybiphenyl-2-yl)-2,2-dimethylpropanenitrile

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

Under a nitrogen atmosphere, to a solution of 3-(2-bromo-5-((tert-butyl(dimethyl)silyl)oxy)phenyl)-2,2-dimethylpropanenitrile (903 mg), 2-fluoro-5-methoxyphenylboronic acid (621 mg), tris(dibenzylideneacetone)dipalladium(0) (45 mg) and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (79 mg) in toluene (10 mL) was added 2.0 M aqueous sodium carbonate solution (3.7 mL), and the mixture was stirred at 90° C. for 3 hr. The reaction mixture was filtered through celite, water was added to the filtrate, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound as a crude product. This compound was used for the next step without further purification.

Workup

  1. filtrationThe reaction mixture was filtered through celite, water
  2. additionwas added to the filtrate
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-ddedf51ad02d4d9794db85c27d74c48d
Source dataset
uspto-grants-2016_07
Patent number
US09382188B2

Reaction notes

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