N-methyl-2-pyrrolidone → 2-Cyano-5-fluoropyridine

HRID 911303Notes

Reaction equation

HRID 911303 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]([C:8]#[N:9])=[N:6][CH:7]=1.[F-:10].[K+].CN1C(=O)CCC1>CCOC(C)=O>[F:10][C:2]1[CH:3]=[CH:4][C:5]([C:8]#[N:9])=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 13387N-methyl-2-pyrrolidone2×HCID 522689Potassium Fluoride2×HCID 38339425-Chloro-2-cyanopyridine

Product 1

HCID 113324532-Cyano-5-fluoropyridineYield 56.6%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Add 5-chloro-pyridine-2-carbonitrile (3.0 g, 21.7 mmol) and potassium fluoride (3.9 g, 67.1 mmol) to a flask containing NMP (75 mL). Heat the mixture to reflux for 16 h. Add additional potassium fluoride (1.0 g, 17.2 mmol) and NMP (10 mL), then continue heating at reflux for 3 h. Cool the mixture, dilute with EtOAc, then wash with saturated NaCl (3×50 mL). Collect the organic layer, concentrate in vacuo and purify by chromatography on silica gel eluting with hexane/EtOAc (20:1) to obtain the desired intermediate (1.5 g, 53%).

Workup

  1. temperatureHeat the mixture
  2. temperatureto reflux for 16 h
  3. temperaturecontinue heating
  4. temperatureat reflux for 3 h
  5. temperatureCool the mixture
  6. washwash with saturated NaCl (3×50 mL)
  7. customCollect the organic layer
  8. concentrationconcentrate in vacuo
  9. custompurify by chromatography on silica gel eluting with hexane/EtOAc (20:1)

Sources & evidence

ORD record
ord-a95b1deea9704c119e2dd95556907e84
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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