Sodium hydride → 2-(3,4-Difluorophenyl)-4-(tetrahydro-2-pyranyloxy)butanenitrile

HRID 355466Notes

Reaction equation

HRID 355466 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]#[N:11])[CH:5]=[CH:6][C:7]=1[F:8].[H-].[Na+].Br[CH2:15][CH2:16][O:17][CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][O:19]1>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([CH:9]([CH2:15][CH2:16][O:17][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)[C:10]#[N:11])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 69572(3,4-Difluorophenyl)acetonitrileHCID 866212-(2-Bromoethoxy)tetrahydro-2H-pyran

Product 1

HCID 224526272-(3,4-Difluorophenyl)-4-(tetrahydro-2-pyranyloxy)butanenitrileYield 54.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 50 g of 3,4-difluorophenyl acetonitrile in 50 ml of THF is added dropwise at 20° C. to a suspension of 14.4 g of 60% sodium hydride in oil in 250 ml of THF, and the reaction mixture is left stirring for three hours at RT. It is cooled in an ice bath, a solution of 68.2 g of 1-bromo-2-(tetrahydro-2-pyranyloxy)ethane in 50 ml of THF is added dropwise and the reaction mixture is left stirring overnight at RT. It is acidified by adding a pH 2 buffer solution, and the THF is then evaporated off under vacuum. The aqueous phase is extracted with ether, the organic phase is washed twice with a pH 4 buffer solution, with water and with saturated NaCl solution and dried over Na2SO4 and the solvent is evaporated off under vacuum. The residue is chromatographed on silica, eluting with toluene and then with a toluene/AcOEt (100:3; v/v) mixture. 50 g of the expected product are obtained.

Workup

  1. waitthe reaction mixture is left
  2. temperatureIt is cooled in an ice bath
  3. waitthe reaction mixture is left
  4. stirringstirring overnight at RT
  5. customthe THF is then evaporated off under vacuum
  6. extractionThe aqueous phase is extracted with ether
  7. washthe organic phase is washed twice with a pH 4 buffer solution, with water and with saturated NaCl solution
  8. dry with materialdried over Na2SO4
  9. customthe solvent is evaporated off under vacuum
  10. customThe residue is chromatographed on silica
  11. washeluting with toluene

Sources & evidence

ORD record
ord-cd3cff164cf4481e84e5e5a23a929a18
Source dataset
uspto-grants-1998_11
Patent number
US05830906

Reaction notes

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