Potassium Carbonate → 3-Ethynyl-5-fluoro-4-methylpyridine

HRID 1502468Notes

Reaction equation

HRID 1502468 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]#[C:9][Si](C)(C)C)=[C:4]([CH3:14])[C:3]=1[F:15].C(=O)([O-])[O-].[K+].[K+]>CC(O)=O.C(OCC)(=O)C.CO.ClCCl.[Zn]>[C:8]([C:5]1[CH:6]=[N:7][CH:2]=[C:3]([F:15])[C:4]=1[CH3:14])#[CH:9]

Participants

8

Reactant 2

HCID 11430Potassium CarbonateHCID 866749802-Chloro-3-fluoro-4-methyl-5-((trimethylsilyl)ethynyl)pyridine

Product 1

HCID 866749813-Ethynyl-5-fluoro-4-methylpyridine

Reagents, catalysts & solvents 5

HCID 23994ZincCatalystHCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 2-(6-chloro-5-fluoro-4-methyl-3-pyridyl)ethynyl-trimethyl-silane (2300 mg, 9.5 mmol) in AcOH (12 mL) was added zinc (1200 mg, 19 mmol). The mixture was heated at 70° C. for 1 hour. The reaction mixture was diluted with ethyl acetate (50 mL), filtered over Celite, evaporated in vacuo and then re-dissolved in ethyl acetate (50 mL) and washed with saturated aqueous sodium bicarbonate solution (20 mL). The organic layer was separated, dried over sodium sulfate, filtered and concentrated in vacuo to provide a residue that was dissolved in MeOH (15 mL) and treated with potassium carbonate (270 mg, 1.9 mmol). The reaction mixture was stirred for 15 minutes at room temperature and then diluted with dichloromethane (50 mL), filtered over Celite, and concentrated in vacuo to provide a residue that was purified by flash chromatography (40 g, Silica, 0-50% diethyl ether in pentane). Desired fractions were combined and evaporated in vacuo to afford the title compound as colorless, crystalline solid (1005 mg, 82%). 1H NMR (400 MHz, CDCl3) δ 8.46 (s, 1H), 8.33 (s, 1H), 3.42 (s, 1H), 2.40 (s, 3H).

Workup

  1. filtrationfiltered over Celite
  2. customevaporated in vacuo
  3. dissolutionre-dissolved in ethyl acetate (50 mL)
  4. washwashed with saturated aqueous sodium bicarbonate solution (20 mL)
  5. customThe organic layer was separated
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto provide a residue that
  10. filtrationfiltered over Celite
  11. concentrationconcentrated in vacuo
  12. customto provide a residue that
  13. customwas purified by flash chromatography (40 g, Silica, 0-50% diethyl ether in pentane)
  14. customevaporated in vacuo

Sources & evidence

ORD record
ord-d61aacfd155e4aea9f28716df114345a
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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