Triethylamine → 2-Fluoro-5-(5-methoxypyridin-3-ylethynyl)-benzonitrile

HRID 606889Notes

Reaction equation

HRID 606889 reaction equation
[C:1]([C:3]1[CH:4]=[N:5][CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1)#[CH:2].[F:11][C:12]1[CH:19]=[CH:18][C:17](I)=[CH:16][C:13]=1[C:14]#[N:15].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>[F:11][C:12]1[CH:19]=[CH:18][C:17]([C:2]#[C:1][C:3]2[CH:4]=[N:5][CH:6]=[C:7]([O:9][CH3:10])[CH:8]=2)=[CH:16][C:13]=1[C:14]#[N:15]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27789282-Fluoro-5-iodobenzonitrileHCID 210973493-Ethynyl-5-methoxypyridine

Product 1

HCID 670476092-Fluoro-5-(5-methoxypyridin-3-ylethynyl)-benzonitrileYield 90%

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, 0.1 mmol), copper (I) iodide (44 mg, 0.23 mmol), and 3-ethynyl-5-methoxypyridine (300 mg, 2.3 mmol), (prepared as described in PREPARATION 10), to a solution of 2-fluoro-5-iodobenzonitrile (670 mg, 2.7 mmol) in triethylamine (3.4 mL, 34 mmol) and heat at 60° C. for 2.75 h. Cool to room temperature and concentrate. Purify the residue by silica gel chromatography, eluting with 100:0 to 80:20 dichloromethane/ethyl acetate followed by a second silica gel chromatography, eluting with 75:25 to 60:40 hexanes:ethyl acetate to give the title compound as a white solid (510 mg, 90%).

Workup

  1. temperatureCool to room temperature
  2. concentrationconcentrate
  3. customPurify the residue by silica gel chromatography
  4. washeluting with 100:0 to 80:20 dichloromethane/ethyl acetate
  5. washeluting with 75:25 to 60:40 hexanes

Sources & evidence

ORD record
ord-7e0beb338e42442d8e7bf97e48221d7a
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

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