Sodium hydride → 2-[4-(1-Methyl-piperidin-4-yl)-butoxy]-isonicotinonitrile

HRID 2420980Notes

Reaction equation

HRID 2420980 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([CH2:8][CH2:9][CH2:10][CH2:11][OH:12])[CH2:4][CH2:3]1.[H-].[Na+].Cl[C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][N:23]=1)[C:19]#[N:20].C([O-])(O)=O.[Na+]>CN(C=O)C.O>[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:16]2[CH:17]=[C:18]([CH:21]=[CH:22][N:23]=2)[C:19]#[N:20])[CH2:4][CH2:3]1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 5686382-Chloro-4-cyanopyridineHCID 230339654-(1-Methyl-piperidin-4-yl)-butan-1-ol

Product 1

HCID 574528642-[4-(1-Methyl-piperidin-4-yl)-butoxy]-isonicotinonitrileYield 28%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of 4-(1-methyl-piperidin-4-yl)-butan-1-ol (1.0 g, 5.85 mmol) in DMF (12 mL) at 0° C. was added NaH (60%; 280 mg, 7.02 mmol). The mixture was warmed to rt for 1 h, then cooled to 0° C. A solution of 2-chloro-isonicotinonitrile (810 mg, 5.85 mmol) in DMF (4 mL) was added dropwise. The mixture was stirred at rt for 18 h, and then was diluted with water (5 mL) and satd. aq. NaHCO3 (25 mL). The mixture was extracted with CHCl3 (3×25 mL), dried (Na2SO4), filtered, and. Purification by Method 1 afforded 440 mg (28%) of a yellow oil.

Workup

  1. temperaturecooled to 0° C
  2. extractionThe mixture was extracted with CHCl3 (3×25 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customPurification by Method 1

Sources & evidence

ORD record
ord-05294fdfb9b44804b0e709efd778103f
Source dataset
uspto-grants-2011_06
Patent number
US07956066B2

Reaction notes

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