2,5-Dibromopyridine → 5-Bromo-2-(3-methoxy-prop-1-ynyl)-pyridine

HRID 217599Notes

Reaction equation

HRID 217599 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[CH3:9][O:10][CH2:11][C:12]#[CH:13]>C(N(CC)CC)C.C(OCC)(=O)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([C:13]#[C:12][CH2:11][O:10][CH3:9])=[N:3][CH:4]=1

Participants

7

Reactant 2

HCID 693532,5-DibromopyridineHCID 693933-Methoxypropyne

Product 1

HCID 225032615-Bromo-2-(3-methoxy-prop-1-ynyl)-pyridineYield 59.6%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2,5-dibromo-pyridine (41, 4.64 g, 19.6 mmol), 3-methoxy-propyne (30, 1.66 mL, 19.7 mmol), and copper(I) iodide (0.084 g, 0.44 mmol) in 61.6 mL of triethylamine was purged with nitrogen, and bis(triphenylphosphine)palladium(II) chloride (0.31 g, 0.44 mmol) was added at 0° C. The resulting mixture was stirred at 0° C. for 1 hour, then at room temperature for 1 hour. The reaction mixture was diluted with ethyl acetate, then washed with water and brine. The organic layer was dried with anhydrous sodium sulfate, filtered and the filtrate concentrated under vacuum. The crude material was purified by silica gel flash chromatography eluting with ethyl acetate and hexane. The appropriate fractions were combined and the solvents removed under vacuum to provide the desired compound (42, 2.64 g).

Workup

  1. additionwas added at 0° C
  2. waitat room temperature for 1 hour
  3. washwashed with water and brine
  4. dry with materialThe organic layer was dried with anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under vacuum
  7. customThe crude material was purified by silica gel flash chromatography
  8. washeluting with ethyl acetate and hexane
  9. customthe solvents removed under vacuum

Sources & evidence

ORD record
ord-e3b5e0cbec874752834aaf1c6e5f504c
Source dataset
uspto-grants-2012_06
Patent number
US08198273B2

Reaction notes

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