Triethylamine → 3-(3-Bromo-4-fluorophenylethynyl)-5-chloropyridine

HRID 606907Notes

Reaction equation

HRID 606907 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([C:8]#[CH:9])[CH:7]=1.[Br:10][C:11]1[CH:16]=[C:15](I)[CH:14]=[CH:13][C:12]=1[F:18].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>[Br:10][C:11]1[CH:16]=[C:15]([C:9]#[C:8][C:6]2[CH:5]=[N:4][CH:3]=[C:2]([Cl:1])[CH:7]=2)[CH:14]=[CH:13][C:12]=1[F:18]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27569802-Bromo-1-fluoro-4-iodobenzeneHCID 235008873-Chloro-5-ethynylpyridine

Product 1

HCID 670474403-(3-Bromo-4-fluorophenylethynyl)-5-chloropyridineYield 82%

Reagents, catalysts & solvents 2

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

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-bromo-1-fluoro-4-iodobenzene, (prepared as described in PREPARATION 43), (0.78 g, 2.6 mmol) in triethylamine (3.3 mL, 33 mmol). Stir at room temperature for 24 h then concentrate. Purify by silica gel chromatography, eluting with 75:25 dichloromethane:hexanes to 100:0 dichloromethane:hexanes to 95:5 dichloromethane:ethyl acetate, followed by a second silica gel chromatography, eluting with 95:5 to 90:10 hexanes:ethyl acetate, to give the title compound as a white solid (560 mg, 82%).

Workup

  1. concentrationthen concentrate
  2. customPurify by silica gel chromatography
  3. washeluting with 75:25 dichloromethane
  4. washeluting with 95:5 to 90:10 hexanes

Sources & evidence

ORD record
ord-44d9321136aa4fd5b109ae23a395cd23
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

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