Sodium hydride → 2-(3-(3,4-Dichlorophenyl)-4-aminobutyl)oxytetrahydropyran

HRID 1585741Notes

Reaction equation

HRID 1585741 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)[CH2:10][NH2:11])[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 156708082-(3-(3,4-Dichlorophenyl)-4-aminobutyl)oxytetrahydropyranYield 69%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 100 g of 3,4-dichlorophenylacetonitrile in 500 ml of THF is added dropwise at 20° C. over 30 minutes to a suspension of 16.5 g of sodium hydride in 200 ml of dry THF, and the reaction mixture is then stirred at RT for 2 hours. It is cooled to -20° C., a solution of 118 g of 1-bromo-2-(tetrahydro-2-pyranyloxy)ethane in 100 ml of THF is added and the mixture is left stirring for 2 hours while allowing the temperature to rise to RT. A solution of 50 g of ammonium chloride in 3 litres of water is then added, the product is extracted with 1.5 litres of ether, and the organic phase is washed with saturated sodium chloride solution, dried over magnesium sulphate and evaporated under vacuum. The residue is chromatographed on silica, eluting with DCM and then with a DCM/AcOEt (95:5; v/v) mixture. 118 g of the expected product are obtained in the form of an oil.

Workup

  1. temperatureIt is cooled to -20° C.
  2. waitthe mixture is left
  3. stirringstirring for 2 hours
  4. customto rise to RT
  5. extractionthe product is extracted with 1.5 litres of ether
  6. washthe organic phase is washed with saturated sodium chloride solution
  7. dry with materialdried over magnesium sulphate
  8. customevaporated under vacuum
  9. customThe residue is chromatographed on silica
  10. washeluting with DCM

Sources & evidence

ORD record
ord-e51e95da11344bc49f8e95c4b55b2dff
Source dataset
uspto-grants-1999_08
Patent number
US05939411

Reaction notes

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