Sodium hydride → HCID 66803442, compound

HRID 627700Notes

Reaction equation

HRID 627700 reaction equation
[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.[H-].[Na+].Cl[C:9]1[CH:10]=[CH:11][C:12]([C:15]#[N:16])=[N:13][CH:14]=1>CN(C=O)C.O>[CH:1]1([CH2:4][O:5][C:9]2[CH:10]=[CH:11][C:12]([C:15]#[N:16])=[N:13][CH:14]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 75644CyclopropanemethanolHCID 38339425-Chloro-2-cyanopyridine

Product 1

HCID 66803442HCID 66803442, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a disposable tube were added cyclopropylmethanol (0.44 ml, 5.41 mmol) in DMF (2 ml) and followed by addition of sodium hydride (60% dispersion in mineral oil) (260 mg, 6.50 mmol) slowly. It was stirred at RT for 15 min. Then 5-chloro-2-cyanopyridine (500 mg, 3.61 mmol) was added. It was stirred at RT for 1 h. Then the reaction mixture was diluted with water and extracted with EtOAc and tBuOMe. The organic extract was washed with brine and dried over MgSO4. The solution was filtered and concentrated to give the crude material as a dark brown oil. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 15% to 30% to 45% EtOAc in heptane, to provide 5-(cyclopropylmethoxy)picolinonitrile as white solid mixed with cyclopropylmethanol. It was washed by heptane/tBuOMe (˜5:1), and the white precipitate was collected by filtration to yield 5-(cyclopropylmethoxy)picolinonitrile (380 mg, 2.181 mmol, 60.4% yield) as white crystals. MS m/z=175.2 (M+H).

Workup

  1. stirringIt was stirred at RT for 1 h
  2. extractionextracted with EtOAc and tBuOMe
  3. extractionThe organic extract
  4. washwas washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationThe solution was filtered
  7. concentrationconcentrated
  8. customto give the crude material as a dark brown oil
  9. customThe crude material was absorbed onto a plug of silica gel
  10. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (40 g)
  11. washeluting with a gradient of 15% to 30% to 45% EtOAc in heptane

Sources & evidence

ORD record
ord-cfdccaaa55d8442a8c517694de3d92be
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

Loading…