Sodium hydride → 4-(6-Fluoro-pyridin-2-yloxymethyl)-benzonitrile

HRID 77933

Reaction equation

HRID 77933 reaction equation
F[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[N:3]=1.[OH:9][CH2:10][C:11]1[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][CH:12]=1.[H-].[Na+]>CN(C)C=O>[F:8][C:4]1[N:3]=[C:2]([O:9][CH2:10][C:11]2[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][CH:12]=2)[CH:7]=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 739342,6-DifluoropyridineHCID 160549p-Cyanobenzyl alcohol

Product 1

HCID 592552944-(6-Fluoro-pyridin-2-yloxymethyl)-benzonitrileYield 61%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To an N,N-dimethylformamide (50 mL) solution of 2,6-difluoropyridine (5 g, 43.4 mmol) and 4-(hydroxymethyl)benzonitrile (8.67 g, 65.1 mmol) was added sodium hydride (2.56 g, 65.1 mmol, 60% in oil) at room temperature. This mixture was stirred for 4 hours at 70° C. This mixture was partitioned into ethyl acetate and water. The organic layer was separated, washed with water, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by NH-silica gel column chromatography (heptane:ethyl acetate=10:1-4:1) to obtain the title compound (5.99 g, 61%).

Workup

  1. customThis mixture was partitioned into ethyl acetate and water
  2. customThe organic layer was separated
  3. washwashed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under a reduced pressure
  7. customthe residue was purified by NH-silica gel column chromatography (heptane:ethyl acetate=10:1-4:1)

Sources & evidence

ORD record
ord-368df5206f534432a401e90a0dc900a3
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Linked notes

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