4-Bromoanisole → 2-(4-Methoxyphenyl)benzonitrile

HRID 1768932

Reaction equation

HRID 1768932 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.C([Li])CCC.Br[C:16]1[CH:23]=[CH:22][CH:21]=[CH:20][C:17]=1[C:18]#[N:19]>O1CCCC1.CCCCCC.CCOCC.[Cl-].[Zn+2].[Cl-].[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:18]([C:17]1[CH:20]=[CH:21][CH:22]=[CH:23][C:16]=1[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1)#[N:19]

Participants

9

Reactant 3

HCID 77304-BromoanisoleHCID 162722-BromobenzonitrileHCID 178418339Butyllithium

Product 1

HCID 13933732-(4-Methoxyphenyl)benzonitrile

Reagents, catalysts & solvents 5

HCID 3007855ZincchlorideCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

To a solution of 4-bromoanisole (18.7 g, 0.1 mol) in anhydrous tetrahydrofuran (200 mL) at -78° C. was added a solution of n-butyl lithium (2.5M, 50 mL) in hexane. After stirring for 0.5 hours, a solution of the zinc chloride (1M, 100 mL) in ether was added. After the mixture was stirred for 1 hour at -78° C., tetrakis (triphenylphosphine) palladium (0.85 g, 0.73 mmol) and 2-bromobenzonitrile (18.2 g, 0.1 mol) were added. The reaction mixture was stirred at room temperature overnight, and then was concentrated in vacuo. The residue was partitioned between ethyl acetate (100 mL) and 1N hydrochloric acid (100 mL). The organic solution was washed with brine and dried over magnesium sulfate. Concentration in vacuo gave crude 4-(2-cyanophenyl)anisole, which was directly used for next reaction. The compound can be triturated with ether to obtain a pure solid product.

Workup

  1. stirringAfter the mixture was stirred for 1 hour at -78° C.
  2. stirringThe reaction mixture was stirred at room temperature overnight
  3. concentrationwas concentrated in vacuo
  4. customThe residue was partitioned between ethyl acetate (100 mL) and 1N hydrochloric acid (100 mL)
  5. washThe organic solution was washed with brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationConcentration in vacuo

Sources & evidence

ORD record
ord-7842e73193204e33a44698038c9ab303
Source dataset
uspto-grants-1995_01
Patent number
US05380719

Linked notes

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