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

HRID 606929Notes

Reaction equation

HRID 606929 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.C(N(CC)CC)C.[C:16]([C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=1)#[CH:17]>C(#N)C.C(OCC)(=O)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:8][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([C:17]#[C:16][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[CH:7]=1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 693693,5-DibromopyridineHCID 5226271-Ethynyl-4-fluorobenzene

Product 1

HCID 670476153-Bromo-5-(4-fluorophenylethynyl)-pyridineYield 51.5%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178419050HCID 178419050, compoundCatalystHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

Heat a suspension of 3,5-dibromopyridine (4.00 g, 16.88 mmol), bis(triphenylphosphine)palladium (II) dichloride (0.59 g, 0.84 mmol) and copper (I) iodide (0.32 g, 1.69 mmol) in triethylamine (4.7 mL, 33.8 mmol) to 80° C. Add a solution of 1-ethynyl-4-fluorobenzene (2.03 g, 16.88 mmol) in acetonitrile (34 mL), stir for 2 h, cool to room temperature and dilute with ethyl acetate. Wash with an aqueous saturated solution of sodium bicarbonate, dry (magnesium sulfate), filter and concentrate. Purify the residue by silica gel chromatography, eluting with a 1% solution of ethyl acetate in 1:1 chloroform:hexanes, and then recrystallize from methanol to give the title compound (2.4 g, 51.5%).

Workup

  1. temperatureHeat
  2. washWash with an aqueous saturated solution of sodium bicarbonate
  3. dry with materialdry (magnesium sulfate)
  4. filtrationfilter
  5. concentrationconcentrate
  6. customPurify the residue by silica gel chromatography
  7. washeluting with a 1% solution of ethyl acetate in 1:1 chloroform
  8. customhexanes, and then recrystallize from methanol

Sources & evidence

ORD record
ord-fc0f881611404a339464bb24cd8f4f6f
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

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