Water → 1-Bromo-3-((4-(difluoromethoxy)phenyl)ethynyl)benzene

HRID 2240982Notes

Reaction equation

HRID 2240982 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:8]#[CH:9])[CH:5]=[CH:6][CH:7]=1.I[C:11]1[CH:16]=[CH:15][C:14]([O:17][CH:18]([F:20])[F:19])=[CH:13][CH:12]=1.CCOC(C)=O.O>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]#[C:9][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH:18]([F:20])[F:19])=[CH:13][CH:12]=2)[CH:3]=1

Participants

8

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 27370081-(Difluoromethoxy)-4-iodobenzeneHCID 114808181-Bromo-3-ethynylbenzene

Product 1

HCID 597903321-Bromo-3-((4-(difluoromethoxy)phenyl)ethynyl)benzene

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-bromophenylacetylene (9.1 g, 50.26 mmol), TEA (22.4 g, 221 mmol, 30.8 mL), bis(triphenylphosphine)dichloropalladium(II) (1.41 g, 2.01 mmol), and CuI (230 mg, 1.2 mmol) in DMF (60 mL) was added 4-iodo(difluoromethoxy)benzene (10.85 g, 40.21 mmol) at room temperature. The reaction mixture had gotten warm after the addition was completed. The mixture was stirred for 4 h then the mixture was portioned between EtOAc and water. The aqueous layer was separated and extracted twice with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated over 40 g Celite. Flash chromatography (SiO2, Hexanes) gave 12 g, 92%, of the title compound as a yellow oil that had crystallized into a solid after being undisturbed for 3d. 1H NMR 500 MHz (DMSO-d6) δ 7.34 (dt, 2H, J=8.92 Hz, 4.70 Hz); 7.42 (t, 1H, 72.99 Hz); 7.54 (t, 1H, J=7.88 Hz); 7.85-7.88 (m, 1H); 7.94-7.97 (m, 1H); 8.00 (dt, 1H, J=8.93 Hz, 4.87 Hz); 8.04 (t, 1H, J=1.80 Hz).

Workup

  1. temperatureThe reaction mixture had gotten warm
  2. additionafter the addition
  3. customThe aqueous layer was separated
  4. extractionextracted twice with EtOAc
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated over 40 g Celite
  8. customFlash chromatography (SiO2, Hexanes) gave 12 g, 92%
  9. customof the title compound as a yellow oil that had crystallized into a solid

Sources & evidence

ORD record
ord-37391d87e3c84585af195f6536878e82
Source dataset
uspto-grants-2010_05
Patent number
US07723368B2

Reaction notes

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