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

HRID 606924Notes

Reaction equation

HRID 606924 reaction equation
[C:1]([C:3]1[CH:4]=[N:5][CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1)#[CH:2].[Br:11][C:12]1[CH:17]=[C:16](I)[CH:15]=[CH:14][C:13]=1[F:19].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:11][C:12]1[CH:17]=[C:16]([C:2]#[C:1][C:3]2[CH:4]=[N:5][CH:6]=[C:7]([O:9][CH3:10])[CH:8]=2)[CH:15]=[CH:14][C:13]=1[F:19]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27569802-Bromo-1-fluoro-4-iodobenzeneHCID 210973493-Ethynyl-5-methoxypyridine

Product 1

HCID 670476803-(3-Bromo-4-fluorophenylethynyl)-5-methoxypyridineYield 94.2%

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 (93 mg, 0.13 mmol), copper (I) iodide (50 mg, 0.26 mmol), and 3-ethynyl-5-methoxypyridine, (prepared as described in PREPARATION 10), (350 mg, 2.6 mmol) to a solution of 2-bromo-1-fluoro-4-iodobenzene, (prepared as described in PREPARATION 43), (1.03 g, 3.4 mmol) in triethylamine (4.0 mL, 39.5 mmol). Stir at room temperature for 20 h then concentrate. Purify 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 (750 mg, 93%).

Workup

  1. concentrationthen concentrate
  2. customPurify by silica gel chromatography
  3. washeluting with 100:0 to 80:20 dichloromethane
  4. washeluting with 75:25 to 60:40 hexanes

Sources & evidence

ORD record
ord-06eb66ef067349d98e98d6443d5f6d8d
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

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