Triethylamine → 3-(3,4-Difluorophenylethynyl)-5-methoxypyridine

HRID 606893Notes

Reaction equation

HRID 606893 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:17]=[CH:16][C:15](I)=[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>[F: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 27244441,2-Difluoro-4-iodobenzeneHCID 210973493-Ethynyl-5-methoxypyridine

Product 1

HCID 670481503-(3,4-Difluorophenylethynyl)-5-methoxypyridineYield 94%

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 (110 mg, 0.15 mmol), copper (I) iodide (57 mg, 0.30 mmol), and 3-ethynyl-5-methoxypyridine, (prepared as described in PREPARATION 10), (400 mg, 3.0 mmol) to a solution of 1,2-difluoro-4-iodobenzene (0.43 mL, 3.6 mmol) in triethylamine (6.3 mL, 45.0 mmol) and heat at 60° C. for 20 h. Cool to room temperature and concentrate. Purify the residue by silica gel chromatography, eluting with 100:0 to 65:35 hexanes:ethyl acetate, followed by a second silica gel chromatography, eluting with 100:0 to 80:20 dichloromethane:ethyl acetate, to give the title compound as a white solid (690 mg, 94%).

Workup

  1. temperatureCool to room temperature
  2. concentrationconcentrate
  3. customPurify the residue by silica gel chromatography
  4. washeluting with 100:0 to 65:35 hexanes
  5. washeluting with 100:0 to 80:20 dichloromethane

Sources & evidence

ORD record
ord-2269d23a63304b4ab47743f694a0cc22
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

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