Sodium hydride → HCID 22452650, compound

HRID 1739113Notes

Reaction equation

HRID 1739113 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)[CH2:10][NH2:11])[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 22452650HCID 22452650, compoundYield 53.7%

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 tirring 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. customthe THF is then evaporated off under vacuum
  5. extractionThe aqueous phase is extracted with ether
  6. washthe organic phase is washed twice with a pH 4 buffer solution, with water and with saturated NaCl solution
  7. dry with materialdried over Na2SO4
  8. customthe solvent is evaporated off under vacuum
  9. customThe residue is chromatographed on silica
  10. washeluting with toluene

Sources & evidence

ORD record
ord-281c99a2f34843d1bd469a7245fde47f
Source dataset
uspto-grants-1999_10
Patent number
US05965580

Reaction notes

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