Triethylamine → 3-Bromo-5-(prop-1-yn-1-yl)pyridine

HRID 539272Notes

Reaction equation

HRID 539272 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.C[Si](C)(C)[C:11]#[C:12][CH3:13].C(N(CC)CC)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1(C)C=CC=CC=1.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[Br:8][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([C:11]#[C:12][CH3:13])[CH:7]=1

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 693693,5-DibromopyridineHCID 803631-(Trimethylsilyl)prop-1-yneHCID 2724141Tetrabutylammonium Fluoride

Product 1

HCID 574665963-Bromo-5-(prop-1-yn-1-yl)pyridineYield 66%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

3,5-Dibromopyridine (30 g, 127 mmol), copper(I) iodide (7.24 g, 38.0 mmol) and tetrakis(triphenylphosphine)palladium(0) (4.39 g, 3.80 mmol) were mixed in toluene (120 mL) under nitrogen atmosphere. 1-(Trimethylsilyl)-1-propyne (26.36 mL, 164.5 mmol), triethylamine (53.0 mL, 380 mmol) and tetra-n-butylammonium fluoride (12.66 mL, 12.66 mmol) were added. The mixture was heated to reflux and stirred under nitrogen overnight. Water (100 mL) was added to the reaction mixture was filtered and the phases separated. The organic phase was washed with 1 M HCl aq. (100 mL). The organic phase was concentrated and dissolved in MeOH (200 mL), filtered and concentrated. The mixture was dissolved in DCM and evaporated with silica gel to dryness, and then transferred to a silica gel column (300 g). The product was eluted with a gradient of EtOAc (0-5%) in heptane. The fractions containing the pure product was combined and evaporated to give the title compound (16.39 g, 66% yield): 1H NMR (500 MHz, CDCl3) δ ppm 2.08 (s, 3 H), 7.82 (t, 1 H), 8.52 (d, 1 H), 8.55 (d, 1 H); MS (APCI+) m/z 197.0 [M+H]|.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux
  3. filtrationwas filtered
  4. customthe phases separated
  5. washThe organic phase was washed with 1 M HCl aq. (100 mL)
  6. concentrationThe organic phase was concentrated
  7. dissolutiondissolved in MeOH (200 mL)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. dissolutionThe mixture was dissolved in DCM
  11. customevaporated with silica gel to dryness
  12. washThe product was eluted with a gradient of EtOAc (0-5%) in heptane
  13. additionThe fractions containing the pure product
  14. customevaporated

Sources & evidence

ORD record
ord-53eae7a8f5af42adb402d2a903aee2b9
Source dataset
uspto-grants-2014_10
Patent number
US08865911B2

Reaction notes

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