Ethyl Acetate → 5-(3,5-Difluorobenzyloxy)nicotinonitrile

HRID 1487384Notes

Reaction equation

HRID 1487384 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:5]=[N:6][CH:7]=[C:8]([CH:11]=1)[C:9]#[N:10].[F:12][C:13]1[CH:14]=[C:15]([CH:18]=[C:19]([F:21])[CH:20]=1)[CH2:16]Br.C(OCC)(=O)C>CC(N(C)C)=O>[F:12][C:13]1[CH:14]=[C:15]([CH:18]=[C:19]([F:21])[CH:20]=1)[CH2:16][O:3][C:4]1[CH:5]=[N:6][CH:7]=[C:8]([CH:11]=1)[C:9]#[N:10]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 5188963,5-Difluorobenzyl bromideHCID 153421425-Hydroxypyridine-3-carbonitrile

Product 1

HCID 682765335-(3,5-Difluorobenzyloxy)nicotinonitrileYield 68%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
0 °C

Procedure

876 mg (2 eq) of sodium hydride is added gradually at 0° C. under nitrogen to a solution of 865 mg of 5-hydroxynicotinonitrile (7.2 mmol) in 15 mL of dimethylacetamide. The mixture is stirred 10 min at 0° C. before adding 2.24 g (1.5 aq) of 3,5-difluorobenzyl bromide. The mixture is placed under stirring for 2.5 additional hours before being diluted in an ethyl acetate fraction and being washed with aqueous fractions. The organic phases are isolated, dried and concentrated. The solid residue obtained is recrystallized in methanol to yield 1.1 g (68% of 5-(3,5-difluorobenzyloxy) nicotinonitrile in the form of a beige powder.

Workup

  1. stirringunder stirring for 2.5 additional hours
  2. washbeing washed with aqueous fractions
  3. customThe organic phases are isolated
  4. customdried
  5. concentrationconcentrated
  6. customThe solid residue obtained
  7. customis recrystallized in methanol

Sources & evidence

ORD record
ord-f3fcfa34abe94d0099b5846281a462be
Source dataset
uspto-grants-2016_08
Patent number
US09428510B2

Reaction notes

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