2-Methyl-3-butyn-2-ol → 2-methyl-4-(3-pyridinyl)-3-butyn-2-ol

HRID 2374188Notes

Reaction equation

HRID 2374188 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[CH3:15][C:16]([OH:20])([C:18]#[CH:19])[CH3:17].C(OCC)(=O)C>COCCOC.[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>[CH3:15][C:16]([OH:20])([C:18]#[C:19][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1)[CH3:17]

Participants

8

Reactant 4

HCID 82582-Methyl-3-butyn-2-olHCID 8471TriethylamineHCID 8857Ethyl Acetate2×HCID 122863-Bromopyridine

Product 1

HCID 27840362-methyl-4-(3-pyridinyl)-3-butyn-2-olYield 40%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
0 °C

Procedure

3-Bromopyridine (3.0 mL, 31 mmol), triethylamine (22 mL, 160 mmol), CuI (1.2 g, 6.2 mmol), and PdCl2(PPh3)2 (1.1 g, 1.5 mmol) were combined in DME (92 mL) and cooled to 0° C. 2-Methyl-3-butyne-2-ol (9.0 mL, 93 mmol) was then added and the reaction was allowed to slowly warm to ambient temperature. The mixture was then heated to 55-60° C. for 16 h. The mixture was filtered through Celite.™., and the pad was washed thoroughly with ethyl acetate. The combined filtrates were washed with brine (3.times.100 mL), dried over MgSO4, and filtered. The solution was concentrated in vacuo, and the residue was purified by column chromatography eluting with 90:10 hexane:ethyl acetate then ethyl acetate to afford 2-methyl-4-(3-pyridinyl-)-3-butyn-2-ol (2.0 g, 40% yield) as a brown oil 1H NMR (CDCl3, 300 MHz) Δ8.76 (br s, 1H), 8.52 (br s, 1H), 7.74-7.70 (m, 1H), 4.08 (br s, 1H), 1.63 (s, 3H). MS (EI ionization) 161 (M+).

Workup

  1. temperatureto slowly warm to ambient temperature
  2. temperatureThe mixture was then heated to 55-60° C. for 16 h
  3. filtrationThe mixture was filtered through Celite
  4. wash, and the pad was washed thoroughly with ethyl acetate
  5. washThe combined filtrates were washed with brine (3.times.100 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationThe solution was concentrated in vacuo
  9. customthe residue was purified by column chromatography
  10. washeluting with 90:10 hexane

Sources & evidence

ORD record
ord-fbaa0e3bd4c1489380ad1e39ddbe8ec1
Source dataset
uspto-grants-2008_12
Patent number
US07462619B2

Reaction notes

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