Potassium Carbonate → HCID 69426314, compound

HRID 1592856Notes

Reaction equation

HRID 1592856 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][NH:15][CH3:16])[CH2:10][CH2:9]1)=O)(C)(C)C.[C:17]([C:19]1[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][N:20]=1)#[N:18].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[ClH:25].[CH3:16][N:15]([CH2:14][CH:11]1[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1)[C:23]1[CH:22]=[CH:21][N:20]=[C:19]([C:17]#[N:18])[CH:24]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 6933424-Chloro-2-pyridinecarbonitrileHCID 21934652tert-Butyl 4-((methylamino)methyl)piperidine-1-carboxylate

Product 1

HCID 69426314HCID 69426314, compoundYield 79.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

A stirred suspension of 1-t-butoxycarbonyl-4-[(methylamino)methyl]piperidine (3.50 g, 15.3 mmol), 2-cyano-4-chloropyridine (2.54 g, 18.3 mmol) and potassium carbonate (4.15 g, 30.0 mmol) in dimethylformamide (38 mL) is heated at 95° C. for 17 hours. Excess dimethylformamide is removed in vacuo and the residue is taken into water and chloroform. The phases are separated and the aqueous phase is extracted into chloroform (×2). The combined organic extracts are washed with 2.5% hydrogen chloride solution, extracted into chloroform (×4) and the combined organic extracts are dried (sodium sulfate), filtered and concentrated in vacuo. The residue is taken into methanol (500 mL) and hydrogen chloride gas is passed through the solution maintaining <20° C. The mixture is kept at this temperature for 3 hours before it is concentrated in vacuo. The residue is taken into water and washed with ethyl acetate (×2). The aqueous phase is made basic by the addition of sodium hydroxide until pH >12 and extracted into ethyl acetate (×8). The combined organic extracts are dried (sodium sulfate), filtered and concentrated in vacuo. The free base is taken into 2.5% hydrogen chloride solution and freeze-dried providing 4-{[(methyl)(2-cyanopyridin-4-yl)amino]methyl}piperidine hydrochloride (3.25 g, 72%).

Workup

  1. customExcess dimethylformamide is removed in vacuo
  2. customThe phases are separated
  3. extractionthe aqueous phase is extracted into chloroform (×2)
  4. washThe combined organic extracts are washed with 2.5% hydrogen chloride solution
  5. extractionextracted into chloroform (×4)
  6. dry with materialthe combined organic extracts are dried (sodium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. temperaturemaintaining <20° C
  10. concentrationis concentrated in vacuo
  11. washwashed with ethyl acetate (×2)
  12. additionThe aqueous phase is made basic by the addition of sodium hydroxide until pH >12
  13. extractionextracted into ethyl acetate (×8)
  14. dry with materialThe combined organic extracts are dried (sodium sulfate)
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo
  17. customfreeze-dried

Sources & evidence

ORD record
ord-3ed9f6f3690e47e18d1f17ee52472388
Source dataset
uspto-grants-2007_11
Patent number
US07294627B2

Reaction notes

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