Triethylamine → 5-(3-Fluorophenylethynyl)-nicotinonitrile

HRID 606836Notes

Reaction equation

HRID 606836 reaction equation
[C:1]([C:3]1[CH:4]=[N:5][CH:6]=[C:7]([CH:10]=1)[C:8]#[N:9])#[CH:2].[F:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14](I)[CH:13]=1.C(N(CC)CC)C>C(OCC)(=O)C.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>[F:11][C:12]1[CH:13]=[C:14]([C:2]#[C:1][C:3]2[CH:4]=[N:5][CH:6]=[C:7]([CH:10]=2)[C:8]#[N:9])[CH:15]=[CH:16][CH:17]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 707251-Fluoro-3-iodobenzeneHCID 224165635-Ethynylnicotinonitrile

Product 1

HCID 670475235-(3-Fluorophenylethynyl)-nicotinonitrileYield 73%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178419050HCID 178419050, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Add bis(triphenylphosphine)palladium (II) dichloride (390 mg, 0.56 mmol), copper (I) iodide (211 mg, 1.11 mmol), and 5-ethynylnicotinonitrile (1.50 g, 11.7 mmol), (prepared essentially as described in PREPARATION 4), to a solution of 1-fluoro-3-iodobenzene (1.31 mL, 11.1 mmol) in triethylamine (21.6 mL, 155 mmol) and heat to 80° C. in a sealed tube for 1.5 h. Cool to room temperature and dilute with ethyl acetate. Wash with a 50% saturated aqueous solution of sodium bicarbonate. Back-extract the aqueous layer three times with dichloromethane and twice with ethyl acetate until the aqueous layer is no longer an emulsion. Combine all organic layers and wash with a saturated aqueous solution of sodium chloride, dry (sodium sulfate), filter and concentrate. Dissolve the residue in ethyl acetate and filter through diatomaceous earth then purify by silica gel chromatography, eluting with a gradient from 95:5 to 80:20 (90:10 hexanes:ethyl acetate):dichloromethane. Further purify by silica gel chromatography, eluting with dichloromethane then 95:5 dichloromethane:ethyl acetate, to give the title compound as a white crystalline solid (1.8 g, 71%).

Workup

  1. custom(prepared essentially
  2. temperatureCool to room temperature
  3. washWash with a 50% saturated aqueous solution of sodium bicarbonate
  4. extractionBack-extract the aqueous layer three times with dichloromethane
  5. washCombine all organic layers and wash with a saturated aqueous solution of sodium chloride
  6. dry with materialdry (sodium sulfate)
  7. filtrationfilter
  8. concentrationconcentrate
  9. dissolutionDissolve the residue in ethyl acetate
  10. filtrationfilter through diatomaceous earth
  11. customthen purify by silica gel chromatography
  12. washeluting with a gradient from 95:5 to 80:20 (90:10 hexanes:ethyl acetate)
  13. customFurther purify by silica gel chromatography
  14. washeluting with dichloromethane

Sources & evidence

ORD record
ord-0302cfe8e50347bebb83e4fa6904c118
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

Loading…