Tetrahydrofuran → 5-(3-Chlorophenylethynyl)-nicotinonitrile

HRID 606835Notes

Reaction equation

HRID 606835 reaction equation
C[Si]([C:5]#[C:6][C:7]1[CH:8]=[N:9][CH:10]=[C:11]([CH:14]=1)[C:12]#[N:13])(C)C.[Cl:15][C:16]1[CH:17]=[C:18](I)[CH:19]=[CH:20][CH:21]=1.C(N(CC)CC)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>[Cl:15][C:16]1[CH:21]=[C:20]([C:5]#[C:6][C:7]2[CH:8]=[N:9][CH:10]=[C:11]([CH:14]=2)[C:12]#[N:13])[CH:19]=[CH:18][CH:17]=1

Participants

8

Reactant 5

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 122691-Chloro-3-iodobenzeneHCID 2724141Tetrabutylammonium FluorideHCID 161156995-[2-(Trimethylsilyl)ethynyl]pyridine-3-carbonitrile

Product 1

HCID 670476655-(3-Chlorophenylethynyl)-nicotinonitrileYield 72.1%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178419050HCID 178419050, compoundCatalyst

Conditions

Temperature
-78 °C

Procedure

Combine 5-Trimethylsilanylethynyl-nicotinonitrile (3.00 g, 15.0 mmol), (prepared as described in PREPARATION 3), bis(triphenylphosphine)palladium (II) dichloride (526 mg, 0.750 mmol), copper (I) iodide (286 mg, 1.50 mmol), and 3-chloroiodobenzene (2.24 μL, 18.0 mmol) in triethylamine (29.3 mL, 210 mmol). Cool the mixture to −78° C. and add a 1 M solution of tetrabutylammonium fluoride in tetrahydrofuran (15.3 mL, 15.3 mmol). After 5 min warn to room temperature and stir 72 h. Filter the reaction through diatomaceous earth, washing with ethyl acetate. Concentrate the filtrate and purify by silica gel chromatography, eluting with a gradient from 95:5 to 70:30 (90:10 hexanes:ethyl acetate):dichloromethane. Further purify by silica gel chromatography, eluting with dichloromethane, then 90:10 dichloromethane:ethyl acetate. Dissolve the chromatographed material (2.91 g) in cyclohexane (120 mL) at 80° C. and cool to room temperature. Collect the recrystallized material via vacuum filtration to give the title compound as a white crystalline solid (2.58 g, 72%).

Workup

  1. filtrationFilter
  2. customthe reaction through diatomaceous earth
  3. washwashing with ethyl acetate
  4. concentrationConcentrate the filtrate
  5. custompurify by silica gel chromatography
  6. washeluting with a gradient from 95:5 to 70:30 (90:10 hexanes:ethyl acetate)
  7. customFurther purify by silica gel chromatography
  8. washeluting with dichloromethane
  9. dissolutionDissolve the chromatographed material (2.91 g) in cyclohexane (120 mL) at 80° C.
  10. temperaturecool to room temperature
  11. customCollect the recrystallized material
  12. filtrationvia vacuum filtration

Sources & evidence

ORD record
ord-4d3b4b2d8d7746b5ba26f6262644e42a
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

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