Dimethylformamide → 3-Cyclobutoxyisonicotinonitrile

HRID 1736598Notes

Reaction equation

HRID 1736598 reaction equation
[H-].[Na+].CN(C=O)C.[CH:8]1([OH:12])[CH2:11][CH2:10][CH2:9]1.Cl[C:14]1[CH:15]=[N:16][CH:17]=[CH:18][C:19]=1[C:20]#[N:21]>O>[CH:8]1([O:12][C:14]2[CH:15]=[N:16][CH:17]=[CH:18][C:19]=2[C:20]#[N:21])[CH2:11][CH2:10][CH2:9]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 76218CyclobutanolHCID 106783063-Chloropyridine-4-carbonitrile

Product 1

HCID 194328303-CyclobutoxyisonicotinonitrileYield 95%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of mineral oil free NaH (0.86 g, 21.4 mmol) and DMF (15 ml) was cooled in an ice-bath and cyclobutanol (1.6 ml, 20.5 mmol) was added in one portion. The mixture was slowly warmed to room temperature and was stirred for 45 minutes. The mixture was once again cooled in an ice-bath and 3-chloro-4-cyanopyridine (2.6 g, 18.6 mmol) was added in one portion. The mixture was warmed to room temperature and was stirred for 3 hours. Water (10 ml) was added and the solvent was removed in vacuo. Water (225 ml) was added to the residue and the mixture was extracted with ether (3×100 mL). The combined organic layers were dried over anhydrous MgSO4, treated with charcoal and removed in vacuo to afford 3.0 g (95%) of 3-cyclobutyloxy-4-cyanopyridine as a white solid.

Workup

  1. temperaturewas cooled in an ice-bath
  2. temperatureThe mixture was once again cooled in an ice-bath
  3. temperatureThe mixture was warmed to room temperature
  4. stirringwas stirred for 3 hours
  5. customthe solvent was removed in vacuo
  6. additionWater (225 ml) was added to the residue
  7. extractionthe mixture was extracted with ether (3×100 mL)
  8. dry with materialThe combined organic layers were dried over anhydrous MgSO4
  9. additiontreated with charcoal
  10. customremoved in vacuo

Sources & evidence

ORD record
ord-f572e8086b2d46fdbda47cbb8b0cc200
Source dataset
uspto-grants-1996_07
Patent number
US05541187

Reaction notes

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