Hydrochloric Acid → 1,1-Dimethylethyl 4-cyano-4-(dimethylamino)-1-piperidinecarboxylate

HRID 2387953Notes

Reaction equation

HRID 2387953 reaction equation
[CH3:1][NH:2][CH3:3].Cl.[CH3:5][NH:6]C.[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][C:18](=O)[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9].Cl.[C-]#N.[K+]>CO.C(OCC)(=O)C.O.CCOC(C)=O.CCCCCC>[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][C:18]([C:5]#[N:6])([N:2]([CH3:3])[CH3:1])[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 674DimethylamineHCID 9032Potassium CyanideHCID 10473Dimethylamine, hydrochlorideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 575047971,1-Dimethylethyl 4-cyano-4-(dimethylamino)-1-piperidinecarboxylateYield 90%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
5 °C

Procedure

500 ml (10 equiv.) of dimethylamine solution and 109.9 g (5 equiv.) of dimethylamine hydrochloride were added to a solution of 50 g (1 equiv.) of tert-butyloxycarbonyl-4-oxopiperidine in 100 ml of methanol, and the mixture was cooled to 5° C. 5 ml (0.1 equiv.) of hydrochloric acid were then added dropwise, over a period of 10 minutes, to the reaction mixture, and stirring was carried out for 60 minutes at room temperature. 48.9 g (3 equiv.) of potassium cyanide were added in portions to the reaction mixture, and stirring was carried out for 24 hours at room temperature. The progress of the reaction was monitored by thin-layer chromatography (50% EtOAc/hexane). When the reaction was complete, 150 ml of water were added to the reaction mixture, and extraction was carried out 3× with 100 ml of ethyl acetate. The combined organic phases were dried with Na2SO4. After removal of the solvent under reduced pressure, crude product was obtained and was recrystallized from hexane. 57 g (90%) of product were obtained in the form of a colourless solid.

Workup

  1. stirringstirring
  2. waitwas carried out for 24 hours at room temperature
  3. dry with materialThe combined organic phases were dried with Na2SO4
  4. customAfter removal of the solvent under reduced pressure
  5. customcrude product was obtained
  6. customwas recrystallized from hexane

Sources & evidence

ORD record
ord-466939467ea54734af35680bb5107872
Source dataset
uspto-grants-2012_09
Patent number
US08269000B2

Reaction notes

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