Reaction #657283

Reaction equation

1-Methoxy-piperidin-4-one

potassium cyanide

cyclopropylamine

hydrochloric acid

→

4-Cyclopropylamino-1-methoxy-piperidine-4-carbonitrile

Solvents

water

diethyl ether

water

methanol

Conditions

Workup

1. 1
   workup.ADDITIONwere then added dropwise at 0° C
2. 2
   TemperatureThe reaction mixture was warmed to room temperature
3. 3
   workup.STIRRINGstirred overnight
4. 4
   Otherthe layers separated
5. 5
   Extractionthe aqueous phase thoroughly extracted with diethyl ether
6. 6
   WashThe combined organic layers were washed with brine
7. 7
   Dryingdried over sodium sulfate
8. 8
   Otherevaporated
9. 9
   OtherThis material was used without further purification in the next step

Procedure

To a solution of cyclopropylamine (1.4 ml, 1.14 g, 20.0 mmol) in methanol (20 ml) at 0° C. was added 1N hydrochloric acid (20 ml, 20.0 mmol) dropwise and the mixture was stirred at room temperature for 30 minutes. 1-Methoxy-piperidin-4-one [prepared according to Journal of Organic Chemistry (1961), 26, 1867-74] (2.58 g, 20.0 mmol), followed 10 minutes later by potassium cyanide (1.3 g, 20.0 mmol) in water (10 ml) were then added dropwise at 0° C. The reaction mixture was warmed to room temperature and stirred overnight, diluted with water and diethyl ether, the layers separated and the aqueous phase thoroughly extracted with diethyl ether. The combined organic layers were washed with brine, dried over sodium sulfate and evaporated. Yield: 3.19 g of 4-cyclopropylamino-1-methoxy-piperidine-4-carbonitrile (title compound P5.2) as an oil. This material was used without further purification in the next step.

Source