Sodium hydride → 2-(3-Cyano-3-(3,4-dichlorophenyl)propyl)oxytetrahydropyran

HRID 1377961Notes

Reaction equation

HRID 1377961 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]#[N:11])[CH:5]=[CH:6][C:7]=1[Cl:8].[H-].[Na+].Br[CH2:15][CH2:16][O:17][CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][O:19]1.[Cl-].[NH4+]>C1COCC1.O>[Cl: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[Cl:8]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 76690(3,4-Dichlorophenyl)acetonitrileHCID 866212-(2-Bromoethoxy)tetrahydro-2H-pyran

Product 1

HCID 156708072-(3-Cyano-3-(3,4-dichlorophenyl)propyl)oxytetrahydropyranYield 69.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 100 g of 3,4-dichlorophenylacetonitrile in 500 ml of THF was added dropwise over 30 minutes to a suspension of 16.5 g of sodium hydride in 200 ml of dry THF at 20° C. The reaction mixture was stirred for 2 hours at RT. It was then cooled to -20° C., and a solution of 118 g of 1-bromo-2-(tetrahydropyran-2-yloxy) ethane in 100 ml of THF was added and the mixture was stirred for 2 hours, allowing the temperature to increase back up to RT. A solution of 50 g of ammonium chloride in 3 liters of water was added, then the mixture was extracted with 1.5 liters of ether, washed with a saturated sodium chloride solution, dried over magnesium sulfate and vacuum evaporated. The residue was chromatographed on silica, eluting with DCM then a DCM/EtOAc (95/5; v/v) mixture. 118 g of the expected product was obtained as an oil which was used as such in the following step.

Workup

  1. temperatureIt was then cooled to -20° C.
  2. stirringthe mixture was stirred for 2 hours
  3. temperatureto increase back up to RT
  4. extractionthe mixture was extracted with 1.5 liters of ether
  5. washwashed with a saturated sodium chloride solution
  6. dry with materialdried over magnesium sulfate and vacuum
  7. customevaporated
  8. customThe residue was chromatographed on silica
  9. washeluting with DCM

Sources & evidence

ORD record
ord-9cc0b2a91a394d458e489c2f79b7e889
Source dataset
uspto-grants-1997_09
Patent number
US05665886

Reaction notes

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