Triethylamine → 5-(5-Chloropyridin-3-ylethynyl)-2-fluorobenzonitrile

HRID 606938Notes

Reaction equation

HRID 606938 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([C:8]#[CH:9])[CH:7]=1.[F:10][C:11]1[CH:18]=[CH:17][C:16](I)=[CH:15][C:12]=1[C:13]#[N:14].C(N(CC)CC)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>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]#[C:9][C:16]2[CH:17]=[CH:18][C:11]([F:10])=[C:12]([CH:15]=2)[C:13]#[N:14])[CH:5]=[N:4][CH:3]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27789282-Fluoro-5-iodobenzonitrileHCID 235008873-Chloro-5-ethynylpyridine

Product 1

HCID 670479015-(5-Chloropyridin-3-ylethynyl)-2-fluorobenzonitrileYield 91%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
60 °C

Procedure

Add bis(triphenylphosphine)palladium (II) dichloride (77 mg, 0.11 mmol), copper (I) iodide (42 mg, 0.22 mmol), and 3-chloro-5-ethynylpyridine, (prepared as described in PREPARATION 27), (300 mg, 2.2 mmol) to a solution of 2-fluoro-5-iodobenzonitrile (650 mg, 2.6 mmol) in triethylamine (4.6 mL, 33 mmol) and heat at 60° C. for 6 h. Cool to room temperature and concentrate. Purify by silica gel chromatography, eluting with 50:50 dichloromethane:hexanes to 90:10 dichloromethane:ethyl acetate, followed by a second silica gel chromatography eluting with 95:5 to 75:25 hexanes:ethyl acetate, to give the title compound as an off-white solid (510 mg, 91%).

Workup

  1. temperatureCool to room temperature
  2. concentrationconcentrate
  3. customPurify by silica gel chromatography
  4. washeluting with 50:50 dichloromethane
  5. washeluting with 95:5 to 75:25 hexanes

Sources & evidence

ORD record
ord-645846654c8d47c99128137bc9461c7c
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

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