4-Piperidinecarboxamide → HCID 19838834, compound

HRID 1639262Notes

Reaction equation

HRID 1639262 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH2:12][C:13]([OH:15])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClC(OCC(C)C)=O.C(N(CC)CC)C.[NH:31]1[CH2:36][CH2:35][CH:34]([C:37]([NH2:39])=[O:38])[CH2:33][CH2:32]1>O1CCCC1>[CH2:1]([O:8][C:9]([NH:11][CH2:12][C:13]([N:31]1[CH2:36][CH2:35][CH:34]([C:37]([NH2:39])=[O:38])[CH2:33][CH2:32]1)=[O:15])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 37724-PiperidinecarboxamideHCID 8471TriethylamineHCID 14349BenzyloxycarbonylglycineHCID 62365Isobutyl chloroformate

Product 1

HCID 19838834HCID 19838834, compoundYield 67.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

62.8 g of N-benzyloxycarbonyl glycine was dissolved in 1000 ml of tetrahydrofuran and the solution was cooled to -15° C., to which 42.3 g of isobutyl chloroformate and then 31.0 g of triethylamine were added dropwise at -15° to -5° C. and stirrd at -10° to -5° C. for 15 minutes. Next, 38.5 g of 4-piperidinecarboxamide was added while maintaining the temperature at -10° to -5° C. The reaction liquid was allowed to stand so as to rise its temperature to room temperature over 2 hours. The insoluble solid was filtered off. This solid was suspended in 500 ml of water, the suspension was stirred for 30 minutes and then the insoluble solid was filtered off. The wet solid was dissolved in 700 ml of ethanol with warming and the solution was concentrated to 200 ml at atmospheric pressure. After the concentrate was allowed to cool, 64.8 g of 1-(N-benzyloxycarbonylglycyl)-4-piperidinecarboxamide having the melting point of 164° to 166° C. was obtained. This was dissolved in 950 ml of methanol and 7 g of 5 % palladium on carbon was added thereto followed by subjecting to the catalytic hydrogenation while introducing hydrogen gas at room temperature. After 4 hours, the catalyst was filtered off and the reaction solution was concentrated to 100 ml. 250 ml of ethyl acetate was added and again the resultant solution was concentrated to 150 ml and allowed to cool so as to obtain the precipitate, which was filtered to obtain the titled compound.

Workup

  1. temperaturewhile maintaining the temperature at -10° to -5° C
  2. customThe reaction liquid
  3. customto room temperature
  4. customover 2 hours
  5. filtrationThe insoluble solid was filtered off
  6. filtrationthe insoluble solid was filtered off
  7. dissolutionThe wet solid was dissolved in 700 ml of ethanol
  8. temperaturewith warming
  9. concentrationthe solution was concentrated to 200 ml at atmospheric pressure
  10. temperatureto cool

Sources & evidence

ORD record
ord-3439d88fbfc64fdc8c7c9d70f6006e98
Source dataset
uspto-grants-1989_11
Patent number
US04883802

Reaction notes

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