Trimethylsilylacetylene → (6-Ethynylpyridin-2-yl)methanol

HRID 1668508Notes

Reaction equation

HRID 1668508 reaction equation
C([O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8](Br)[N:7]=1)(=O)C.C[Si](C)(C)[C:15]#[CH:16]>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.[Cu]I.C(N(CC)CC)C>[C:15]([C:8]1[N:7]=[C:6]([CH2:5][OH:4])[CH:11]=[CH:10][CH:9]=1)#[CH:16]

Participants

6

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 86621821HCID 86621821, compound

Product 1

HCID 56972612(6-Ethynylpyridin-2-yl)methanolYield 15.9%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Procedure

To a round-bottom flask was added 2.3 g of 6-bromopyridin-2-ylmethyl acetate, 1.18 g of trimethyl silylacetylene, 210 mg of bis(triphenylphosphine)-palladium(II) chloride, 114 mg of copper(I) iodide and 12 mL of triethylamine, and then the mixture was heated to reflux under argon atmosphere for 5 hours. After allowing to cool, the mixture was concentrated to dryness under reduced pressure, thereto water was added, and the mixture was extracted with ethyl acetate. The organic layer was concentrated under reduced pressure, 7 mL of methanol and 30 mL of 1N aqueous potassium hydroxide were added to the residue, and the mixture was stirred for 1 hour. The reaction mixture was acidified with 1N hydrochloric acid and concentrated under reduced pressure. The concentrated solution was basified with potassium carbonate, and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and then the solvent was removed off under reduced pressure. The product was purified by chromatography on silica gel (hexane-ethyl acetate=4:1) to give 212 mg of (6-ethynylpyridin-2-yl)methanol as a white powder.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux under argon atmosphere for 5 hours
  3. temperatureto cool
  4. concentrationthe mixture was concentrated to dryness under reduced pressure
  5. additionwater was added
  6. extractionthe mixture was extracted with ethyl acetate
  7. concentrationThe organic layer was concentrated under reduced pressure, 7 mL of methanol and 30 mL of 1N aqueous potassium hydroxide
  8. additionwere added to the residue
  9. concentrationconcentrated under reduced pressure
  10. extractionextracted with ethyl acetate
  11. washThe organic layer was washed with brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. customthe solvent was removed off under reduced pressure
  14. customThe product was purified by chromatography on silica gel (hexane-ethyl acetate=4:1)

Sources & evidence

ORD record
ord-cf7d6805a2b5449e9c9617baa04f188d
Source dataset
uspto-grants-2011_08
Patent number
US07989446B2

Reaction notes

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