Hydrochloric Acid → 4-Cyclopropylamino-1-methoxy-piperidine-4-carbonitrile

HRID 1473761Notes

Reaction equation

HRID 1473761 reaction equation
[CH:1]1([NH2:4])[CH2:3][CH2:2]1.Cl.[CH3:6][O:7][N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1.[C-:15]#[N:16].[K+]>CO.O.C(OCC)C>[CH:1]1([NH:4][C:11]2([C:15]#[N:16])[CH2:12][CH2:13][N:8]([O:7][CH3:6])[CH2:9][CH2:10]2)[CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 9032Potassium CyanideHCID 69828CyclopropylamineHCID 199366531-Methoxypiperidin-4-one

Product 1

HCID 585379054-Cyclopropylamino-1-methoxy-piperidine-4-carbonitrile

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 3283Diethyl EtherSolvent

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.

Workup

  1. additionwere then added dropwise at 0° C
  2. temperatureThe reaction mixture was warmed to room temperature
  3. stirringstirred overnight
  4. customthe layers separated
  5. extractionthe aqueous phase thoroughly extracted with diethyl ether
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over sodium sulfate
  8. customevaporated
  9. customThis material was used without further purification in the next step

Sources & evidence

ORD record
ord-7595bba0594a4f8fb2ba767a1a55ad7d
Source dataset
uspto-grants-2015_04
Patent number
US09018135B2

Reaction notes

Loading…