Reaktion #336114

Reaktionsgleichung

4-(3-piperidinomethylphenoxy)butyronitrile

4-(3-piperidinomethylphenoxy)butyronitrile

LiAlH4

3-piperidinomethylphenol

NaOH

4-chlorobutyronitrile

sodium

→

4-(3-piperidinomethylphenoxy)butaneamine

Lösungsmittel

ether

water

ethanol

ethanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthe batch is heated
2. 2
   Temperaturunder reflux overnight with the exclusion of moisture
3. 3
   Temperaturto cool
4. 4
   Filtrationis filtered
5. 5
   Einengenconcentrated to dryness in vacuo
6. 6
   Waschenwashed with 10% NaOH and water
7. 7
   TrocknenDrying over Na2SO4
8. 8
   Sonstigecan be used in the subsequent reaction without further purification
9. 9
   TemperaturWhile cooling with ice
10. 10
    workup.STIRRINGAfter stirring for 40 min at room temperature the batch
11. 11
    workup.STIRRINGStirring
12. 12
    Filtrationthe batch is suction-filtered
13. 13
    Waschenthe precipitate is washed several times with ether
14. 14
    WaschenThe filtrate is washed with water
15. 15
    Trocknendried over Na2SO4
16. 16
    Filtrationfiltered
17. 17
    Einengenconcentrated to dryness in vacuo

Vorschrift

4.6 g (0.2 mol) of sodium are dissolved in anhydrous ethanol and 38.24 g (0.2 mol) of 3-piperidinomethylphenol [DE-A-2 917 026, Glaxo] are added thereto. After the dropwise addition of 20.71 g (0.2 mol) of 4-chlorobutyronitrile in ethanol, the batch is heated under reflux overnight with the exclusion of moisture. It is then allowed to cool, is filtered, and concentrated to dryness in vacuo. The resulting oil is taken up in ether and washed with 10% NaOH and water. Drying over Na2SO4 and concentrating yield 35.5 g (0.14 mol) of 4-(3-piperidinomethylphenoxy)butyronitrile in the form of an oil that can be used in the subsequent reaction without further purification. While cooling with ice and stirring, 59.9 mmol of 4-(3-piperidinomethylphenoxy)butyronitrile are introduced slowly into a suspension of 2.98 g (78.4 mmol) of LiAlH4 in 140 ml of anhydrous ether. After stirring for 40 min at room temperature the batch is hydrolysed, while cooling with ice, with 10 ml of water-saturated ether and 7 ml of 10% NaOH. Stirring is continued for 30 min, and then the batch is suction-filtered and the precipitate is washed several times with ether. The filtrate is washed with water, dried over Na2SO4, filtered and concentrated to dryness in vacuo to yield 4-(3-piperidinomethylphenoxy)butaneamine in the form of a low-viscosity brown oil that can be used in the subsequent reaction without further purification. The equimolar amount of 4-(3-piperidinomethylphenoxy)butaneamine is added while stirring to a suspension of N-cyanodiphenylimidocarbonate in 100 ml of diethyl ether. After stirring for approx. 15 min, the product, N-cyano-O-phenyl-N'-[4-(3-piperidinomethylphenoxy)butyl]isourea, precipitates copiously, or it crystallises when the solution is concentrated. The product is suction-filtered, washed with diethyl ether and dried.

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