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

HRID 1611662Notes

Reaction equation

HRID 1611662 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([CH2:11][C:12]#[N:13])[CH:7]=[CH:8][C:9]=1[Cl:10].Br[CH2:15][CH2:16][O:17][CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][O:19]1>C1COCC1>[C:12]([CH:11]([C:6]1[CH:7]=[CH:8][C:9]([Cl:10])=[C:4]([Cl:3])[CH:5]=1)[CH2:15][CH2:16][O:17][CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][O:19]1)#[N:13]

Participants

5

Reactant 3

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

Product 1

HCID 156708072-(3-Cyano-3-(3,4-dichlorophenyl)propyl)oxytetrahydropyranYield 48.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (57.4 g, 60% dispersion in oil, 1.43 mol) was added to a 3 L, 3-necked flask (fitted with mechanical stirrer, exit needle and condenser) and suspended in THF (900 ml). A solution of 3,4-dichlorophenylacetonitrile (257 g, 1.38 mol) in THF (400 ml) was added to the ice-cooled flask via cannula over a period of 1 hour. The mixture was then stirred at room temperature for 1.5 hours during which time there was vigorous gas evolution. The reaction mixture was then ice-cooled and 2-(2-bromoethyl)oxytetrahydropyran (288.5 g, 1.38 mol) was added via teflon cannula under nitrogen pressure over a period of 30 mins. After 40 hours the reaction mixture was quenched with ammonium chloride (10 ml), concentrated (to remove the THF) and water was added. The mixture was extracted with DCM and the organic extracts dried (Na2SO4), concentrated and distilled under reduced pressure (174° C., 100 mtorr) to give an oil. This residue was purified by flash column chromatography (hexane to 1:1, hexane: DCM) to give 2-(3-cyano-3-[3,4-dichlorophenyl]propyl)oxytetrahydropyran as an oil (210 g, 0.67 mol).

Workup

  1. temperaturecooled flask via cannula over a period of 1 hour
  2. temperatureice-cooled
  3. customAfter 40 hours the reaction mixture was quenched with ammonium chloride (10 ml)
  4. concentrationconcentrated (
  5. customto remove the THF) and water
  6. additionwas added
  7. extractionThe mixture was extracted with DCM
  8. dry with materialthe organic extracts dried (Na2SO4)
  9. concentrationconcentrated
  10. distillationdistilled under reduced pressure (174° C., 100 mtorr)
  11. customto give an oil
  12. customThis residue was purified by flash column chromatography (hexane to 1:1, hexane: DCM)

Sources & evidence

ORD record
ord-0dad337e69114d5bb7ba07b798ca9703
Source dataset
uspto-grants-2006_01
Patent number
US06989393B2

Reaction notes

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