3-Bromopyridine → 5-(3-Pyridinyl)-4-pentyn-1-ol

HRID 1044894Notes

Reaction equation

HRID 1044894 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[CH2:8]([OH:13])[CH2:9][CH2:10][C:11]#[CH:12]>C(N(CC)CC)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I>[N:4]1[CH:5]=[CH:6][CH:7]=[C:2]([C:12]#[C:11][CH2:10][CH2:9][CH2:8][OH:13])[CH:3]=1

Participants

6

Reactant 2

HCID 122863-BromopyridineHCID 793464-Pentyn-1-ol

Product 1

HCID 107970615-(3-Pyridinyl)-4-pentyn-1-olYield 90.5%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8471TriethylamineSolvent

Procedure

3-Bromopyridine (5.4 g, 34.2 mmol) was dissolved in triethylamine (10 ml) and degassed under nitrogen. 4-Pentyn-1-ol (3.50 ml, 37.6 mmol) was added followed by bis(triphenylphosphine)palladium (II) chloride (0.245 g, 0.349 mmol) and copper(I)iodide (0.136 g, 0.714 mmol) and the resulting mixture was stirred and heated under reflux for 20 mins. when a dark brown sludge was obtained. The mixture was cooled to rt and partitioned between EtOAc (200 ml) and water (50 ml). The aqueous phase was extracted further with EtOAc (2×100 ml); the combined organic extracts were dried (Na2SO4), filtered and evaporated in vacuo. The material was purified by column chromatography. The sample was loaded in dichloromethane and purified on silica (Si) 100 g using a gradient of 0-100% ethyl acetate in cyclohexane over 60 mins on the Flashmaster II. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a yellow oil (4.99 g).

Workup

  1. customdegassed under nitrogen
  2. temperatureheated
  3. temperatureunder reflux for 20 mins
  4. customwhen a dark brown sludge was obtained
  5. custompartitioned between EtOAc (200 ml) and water (50 ml)
  6. extractionThe aqueous phase was extracted further with EtOAc (2×100 ml)
  7. dry with materialthe combined organic extracts were dried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated in vacuo
  10. customThe material was purified by column chromatography
  11. custompurified on silica (Si) 100 g
  12. customover 60 mins
  13. customevaporated in vacuo

Sources & evidence

ORD record
ord-441ea7ac23514c07b21229ab6fce8077
Source dataset
uspto-grants-2013_10
Patent number
US08563717B2

Reaction notes

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