Tetrahydrofuran → 3-Ethynyl-4-fluorophthalonitrile

HRID 1851140Notes

Reaction equation

HRID 1851140 reaction equation
[F:1][C:2]1[C:3]([C:12]#[C:13][Si](C)(C)C)=[C:4]([C:10]#[N:11])[C:5](=[CH:8][CH:9]=1)[C:6]#[N:7].C1COCC1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>O>[C:12]([C:3]1[C:2]([F:1])=[CH:9][CH:8]=[C:5]([C:6]#[N:7])[C:4]=1[C:10]#[N:11])#[CH:13]

Participants

5

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 2724141Tetrabutylammonium FluorideHCID 86709187HCID 86709187, compound

Product 1

HCID 867091973-Ethynyl-4-fluorophthalonitrileYield 30%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 4-fluoro-3-((trimethylsilyl)ethynyl)phthalonitrile (Example 40C) (0.302 g, 1.246 mmol) in anhyd THF (5 mL) was added a solution of TBAF in THF (1.246 mL, 1.246 mmol), dropwise. The resulting black mixture was stirred at rt under N2 for 5 min. The mixture was poured into water and extracted with EtOAc (×3). Combined organics were washed (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 3-ethynyl-4-fluorophthalonitrile (0.0635 g, 30% yield) as a tan solid: 1H NMR (400 MHz, CDCl3) δ 7.79 (dd, J=8.7, 4.7 Hz, 1H), 7.49 (dd, J=8.7, 8.0 Hz, 1H), 3.86 (s, 1H); MS (GCMS EI) m/z 170 ([M]+, 100%).

Workup

  1. extractionextracted with EtOAc (×3)
  2. washCombined organics were washed (water, brine)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by low pressure liquid chromatography (silica gel, EtOAc/hexanes, gradient elution)

Sources & evidence

ORD record
ord-59a6831b5bad4c39be9129b5daac32fa
Source dataset
uspto-grants-2015_02
Patent number
US08957104B2

Reaction notes

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