Sodium hydride → 2,6-Difluoro-4-[2-(2-naphthalenyloxy) ethoxy]benzonitrile

HRID 2225784Notes

Reaction equation

HRID 2225784 reaction equation
[F:1][C:2]1[CH:9]=[C:8]([OH:10])[CH:7]=[C:6]([F:11])[C:3]=1[C:4]#[N:5].[H-].[Na+].CS(O[CH2:19][CH2:20][O:21][C:22]1[CH:31]=[CH:30][C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=1)(=O)=O>CN(C)C=O>[F:1][C:2]1[CH:9]=[C:8]([O:10][CH2:19][CH2:20][O:21][C:22]2[CH:31]=[CH:30][C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH:23]=2)[CH:7]=[C:6]([F:11])[C:3]=1[C:4]#[N:5]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27787742,6-Difluoro-4-hydroxybenzonitrileHCID 190043832-(2-Naphthyloxy)ethyl methanesulfonate

Product 1

HCID 190045042,6-Difluoro-4-[2-(2-naphthalenyloxy) ethoxy]benzonitrileYield 69%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A stirred mixture of 2,6-difluoro-4-hydroxybenzonitrile (3 g) in dimethylformamide (30 mL) under argon was treated with 55% sodium hydride (0.842 g), stirred for 30 minutes and treated with 2-(2-naphthalenyloxy)ethyl methanesulfonate (5.1 g). The mixture was heated at 60° C. overnight and evaporated to dryness. The residue was mixed with water and excess sodium hydroxide solution, the product was extracted twice with dichloromethane, and the organic layers were washed with water. The combined organic layers were dried (Na2SO4), filtered, and evaporated. The crude material was purified by HPLC (dichloromethane-hexane 2:1) and crystallized from dichloromethane-hexane to provide 4.3 g of 2,6-difluoro-4-[2-(2-naphthalenyloxy) ethoxy]benzonitrile as a colorless solid, mp 148°-149° C.

Workup

  1. customevaporated to dryness
  2. additionThe residue was mixed with water and excess sodium hydroxide solution
  3. extractionthe product was extracted twice with dichloromethane
  4. washthe organic layers were washed with water
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude material was purified by HPLC (dichloromethane-hexane 2:1)
  9. customcrystallized from dichloromethane-hexane

Sources & evidence

ORD record
ord-3ace71eeecc24610b68e316fb5845da2
Source dataset
uspto-grants-1994_09
Patent number
US05344843

Reaction notes

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