Tetrahydrofuran → 3-Pyridin-3-ylethynyl-benzonitrile

HRID 606839Notes

Reaction equation

HRID 606839 reaction equation
I[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.C[Si]([C:12]#[C:13][C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=1)[C:17]#[N:18])(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1>C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C(N(CC)CC)C>[N:4]1[CH:5]=[CH:6][CH:7]=[C:2]([C:12]#[C:13][C:14]2[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=2)[C:17]#[N:18])[CH:3]=1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 707143-IodopyridineHCID 2724141Tetrabutylammonium FluorideHCID 225703183-[(Trimethylsilyl)ethynyl]benzonitrile

Product 1

HCID 670477283-Pyridin-3-ylethynyl-benzonitrileYield 71%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178419050HCID 178419050, compoundCatalystHCID 8471TriethylamineSolvent

Procedure

Add triethylamine (5 mL) to a stirring mixture of 3-iodopyridine (1.03 g, 5.03 mmol), bis(triphenylphosphine)palladium (II) dichloride (176 mg, 0.252 mmol), copper (I) iodide (96 mg, 0.503 mmol), and 3-trimethylsilanylethynylbenzonitrile, (prepared essentially as described in PREPARATION 5), (1.0 g, 5.03 mmol) at −78° C. After about 3 min, add a 1 M solution of tetrabutylammonium fluoride in tetrahydrofuran (5.03 mL, 5.03 mmol) in one portion, warm to room temperature and stir overnight. Filter the reaction mixture through fluted filter paper and concentrate. Dissolve the residue in ethyl acetate, wash sequentially with a saturated solution of aqueous sodium bicarbonate, a saturated solution of aqueous sodium chloride, dry (sodium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 0:100 to 40:60 ethyl acetate:hexanes, followed by a second silica gel chromatography, eluting with 0:100 to 40:60 ethyl acetate:dichloromethane), to give the title product as a yellow solid (730 mg, 71%).

Workup

  1. custom(prepared essentially
  2. customas described in PREPARATION 5), (1.0 g, 5.03 mmol) at −78° C
  3. filtrationFilter the reaction mixture through fluted filter paper
  4. concentrationconcentrate
  5. dissolutionDissolve the residue in ethyl acetate
  6. washwash sequentially with a saturated solution of aqueous sodium bicarbonate
  7. dry with materiala saturated solution of aqueous sodium chloride, dry (sodium sulfate)
  8. filtrationfilter
  9. concentrationconcentrate
  10. custompurify (silica gel chromatography
  11. washeluting with 0:100 to 40:60 ethyl acetate
  12. washeluting with 0:100 to 40:60 ethyl acetate

Sources & evidence

ORD record
ord-25e937c8e8374d68a87c6199d77ed9ba
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

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