Sodium Carbonate → 1-((4-((Tert-butyl(dimethyl)silyl)oxy)-2'-fluoro-5'-methoxybiphenyl-2-yl)methyl)cyclopentanecarbonitrile

HRID 1049543Notes

Reaction equation

HRID 1049543 reaction equation
Br[C:2]1[CH:15]=[CH:14][C:13]([O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])=[CH:12][C:3]=1[CH2:4][C:5]1([C:10]#[N:11])[CH2:9][CH2:8][CH2:7][CH2:6]1.[F:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][C:26]=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].O>[Si:17]([O:16][C:13]1[CH:14]=[CH:15][C:2]([C:26]2[CH:27]=[C:28]([O:31][CH3:32])[CH:29]=[CH:30][C:25]=2[F:24])=[C:3]([CH2:4][C:5]2([C:10]#[N:11])[CH2:9][CH2:8][CH2:7][CH2:6]2)[CH:12]=1)([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 41572112-Fluoro-5-methoxyphenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 1317360231-(2-Bromo-5-((tert-butyl(dimethyl)silyl)oxy)benzyl)cyclopentanecarbonitrile

Product 1

HCID 1317360241-((4-((Tert-butyl(dimethyl)silyl)oxy)-2'-fluoro-5'-methoxybiphenyl-2-yl)methyl)cyclopentanecarbonitrile

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

Under a nitrogen atmosphere, to a solution of 1-(2-bromo-5-((tert-butyl(dimethyl)silyl)oxy)benzyl)cyclopentanecarbonitrile (471 mg), 2-fluoro-5-methoxyphenylboronic acid (361 mg), tris(dibenzylideneacetone)dipalladium(0) (23 mg) and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (39 mg) in toluene (5.0 mL) was added 2.0M aqueous sodium carbonate solution (1.8 mL), and the mixture was stirred at 90° C. for 1 hr. Water was added to the reaction mixture, 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 a crude product of the title compound. The obtained crude product was directly used for the next step.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-b21ee3b5fcd54e0ca978ea984e4823a4
Source dataset
uspto-grants-2016_07
Patent number
US09382188B2

Reaction notes

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