Tetrahydrofuran → 5-Ethynyl-2-methylpyridine

HRID 1927212Notes

Reaction equation

HRID 1927212 reaction equation
C1COCC1.BrC1C=CC(C)=NC=1.[CH3:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]#[C:22][Si](C)(C)C)=[CH:17][N:16]=1.C(=O)([O-])[O-].[K+].[K+]>O.C(O)C>[C:21]([C:18]1[CH:19]=[CH:20][C:15]([CH3:14])=[N:16][CH:17]=1)#[CH:22]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 12010205-Bromo-2-methylpyridineHCID 155537632-Methyl-5-((trimethylsilyl)ethynyl)pyridine

Product 1

HCID 6381975-Ethynyl-2-methylpyridine

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a NMP solution (20 mL) of 5-bromo-2-methyl-pyridine (1.0 g) were added trimethylsilylacetylene (1.2 mL), tetrakis(triphenylphosphine)palladium(0) (130 mg), copper(I) iodide (44 mg), and N,N-diisopropylethylamine (2.0 mL), which was stirred under a nitrogen atmosphere for 2 hours at 65° C. Water was added at room temperature to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and filtered, after which the solvent was evaporated from the filtrate under a reduced pressure. The residue was purified by silica gel column chromatography (heptane:ethyl acetate=5:1) to obtain a mixture (810 mg) of 5-bromo-2-methyl-pyridine and 2-methyl-5-trimethylsilanylethynyl-pyridine. Then, to a solution of THF (10 mL) and ethanol (5 mL) of the mixture (810 mg) of 5-bromo-2-methyl-pyridine and 2-methyl-5-trimethylsilanylethynyl-pyridine was added potassium carbonate (1.2 g) at room temperature, which was stirred for 2 hours and 30 minutes at room temperature. Water was added at room temperature to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and filtered, after which the solvent was evaporated from the filtrate under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=5:1) to obtain the titled compound (55 mg).

Workup

  1. extractionwas then extracted with ethyl acetate
  2. washThe organic layer was washed with water and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customafter which the solvent was evaporated from the filtrate under a reduced pressure
  6. customthe residue was purified by silica gel column chromatography (heptane:ethyl acetate=5:1)

Sources & evidence

ORD record
ord-119019601e8540d6baf6b889ff90fc74
Source dataset
uspto-grants-2012_05
Patent number
US08183264B2

Reaction notes

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