Potassium Cyanide → 4-Hydroxyamino-1-methoxy-piperidine-4-carbonitrile

HRID 1473769Notes

Reaction equation

HRID 1473769 reaction equation
[CH3:1][O:2][N:3]1[CH2:8][CH2:7][C:6](=[N:9][OH:10])[CH2:5][CH2:4]1.P([O-])(O)(O)=O.[K+].[C-:17]#[N:18].[K+]>O>[OH:10][NH:9][C:6]1([C:17]#[N:18])[CH2:7][CH2:8][N:3]([O:2][CH3:1])[CH2:4][CH2:5]1

Participants

5

Reactant 3

HCID 9032Potassium CyanideHCID 516951Monobasic potassium phosphate2×HCID 584280071-Methoxy-piperidin-4-one oxime

Product 1

HCID 866574644-Hydroxyamino-1-methoxy-piperidine-4-carbonitrile

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

To a suspension of 1-methoxy-piperidin-4-one oxime (240 g, 1.66 mol) and potassium dihydrogen phosphate (792.9 g, 5.83 mol) in water (200 ml) at 0-5° C. was added a solution of potassium cyanide (195.1 g, 3.0 mol) in water (200 ml) dropewise (caution!). The reaction mixture was stirred at room temperature overnight (stoppered flask), treated with another portion of potassium dihydrogen phosphate (79.3 g, 0.58 mol) and further stirred at room temperature over another night. The mixture was flushed with nitrogen, the semi-solid removed by filtration and dissolved in ethyl acetate. The aqueous layer was extracted twice with ethyl acetate, all organic layers combined, washed with water and brine, dried over sodium sulfate and concentrated. The residue was triturated with cold diethyl ether, filtered and dried. Yield: 230.8 g of 4-hydroxyamino-1-methoxy-piperidine-4-carbonitrile as a tan solid, mp 130-131° C.

Workup

  1. stirringfurther stirred at room temperature over another night
  2. customThe mixture was flushed with nitrogen
  3. customthe semi-solid removed by filtration
  4. dissolutiondissolved in ethyl acetate
  5. extractionThe aqueous layer was extracted twice with ethyl acetate
  6. washwashed with water and brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customThe residue was triturated with cold diethyl ether
  10. filtrationfiltered
  11. customdried

Sources & evidence

ORD record
ord-a716cde1ffed4402ac84d05757851dba
Source dataset
uspto-grants-2015_04
Patent number
US09018135B2

Reaction notes

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