Tetrahydrofuran → ((2,3-Dibromo-6-fluorophenyl)ethynyl)trimethylsilane

HRID 1851129Notes

Reaction equation

HRID 1851129 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[C:4](I)[C:3]=1[Br:10].C1COCC1.[C:16]([Si:18]([CH3:21])([CH3:20])[CH3:19])#[CH:17]>CCOC(C)=O.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:10][C:3]1[C:2]([Br:1])=[CH:7][CH:6]=[C:5]([F:8])[C:4]=1[C:17]#[C:16][Si:18]([CH3:21])([CH3:20])[CH3:19]

Participants

7

Reactant 3

HCID 8028TetrahydrofuranHCID 66111TrimethylsilylacetyleneHCID 867091851,2-Dibromo-4-fluoro-3-iodobenzene

Product 1

HCID 86709184((2,3-Dibromo-6-fluorophenyl)ethynyl)trimethylsilaneYield 79.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

A thick-walled glass vessel was charged with 1,2-dibromo-4-fluoro-3-iodobenzene (8.31 g, 21.88 mmol), Pd(PPh3)2Cl2 (0.768 g, 1.094 mmol), and CuI (0.292 g, 1.532 mmol) and sealed with a rubber septum. Anhyd THF (30 mL) and DIPA (30.8 mL, 219 mmol) were added via syringe and the mixture was degassed 10 min by sparging with N2 while immersed in an ultrasonic bath. Ethynyltrimethylsilane (3.40 mL, 24.07 mmol) was added via syringe and the septum was replaced with a PTFE bushing. The mixture was stirred in an oil bath at 40° C. After 40 h, the mixture was cooled, diluted with EtOAc and filtered through a pad of Celite. The filtrate was washed (satd NH4Cl×2, water, brine), dried over Na2SO4 and concentrated in vacuo. The residue was purified by low pressure liquid chromatography (silica gel, EtOAc/hexanes, gradient elution) affording ((2,3-dibromo-6-fluorophenyl)ethynyl)trimethylsilane (6.08 g, 17.37 mmol, 79% yield) as a yellow oil: 1H NMR (400 MHz, CDCl3) δ 7.53 (dd, J=8.9, 5.4 Hz, 1H), 6.95 (dd, J=8.9, 8.1 Hz, 1H), 0.29 (s, 9H); MS (GCMS EI) m/z 348 ([M]+, Br isotopes, 18%), 350 ([M]+, Br isotopes, 34%), 352 ([M]+, Br isotopes, 18%), 333 ([M-CH3]+, Br isotopes, 56%), 335 ([M-CH3]+, Br isotopes, 100%), 337 ([M-CH3]+, Br isotopes, 54%).

Workup

  1. customsealed with a rubber septum
  2. customthe mixture was degassed 10 min
  3. customby sparging with N2
  4. customwhile immersed in an ultrasonic bath
  5. temperaturethe mixture was cooled
  6. filtrationfiltered through a pad of Celite
  7. washThe filtrate was washed (satd NH4Cl×2, water, brine)
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by low pressure liquid chromatography (silica gel, EtOAc/hexanes, gradient elution)

Sources & evidence

ORD record
ord-9346972a12ce4818a2eec53723aff655
Source dataset
uspto-grants-2015_02
Patent number
US08957104B2

Reaction notes

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