Acetic Acid → 4-Benzyloxycarbonyl-1-[1-(4-pyridyl)-4-piperidinylamino]-2-piperazinone

HRID 2086234Notes

Reaction equation

HRID 2086234 reaction equation
[NH2:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:4][C:3]1=[O:18].[N:19]1[CH:24]=[CH:23][C:22]([N:25]2[CH2:30][CH2:29][C:28](=O)[CH2:27][CH2:26]2)=[CH:21][CH:20]=1.C(O)(=O)C.[Na]>C(O)C.CO>[CH2:11]([O:10][C:8]([N:5]1[CH2:6][CH2:7][N:2]([NH:1][CH:28]2[CH2:27][CH2:26][N:25]([C:22]3[CH:23]=[CH:24][N:19]=[CH:20][CH:21]=3)[CH2:30][CH2:29]2)[C:3](=[O:18])[CH2:4]1)=[O:9])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5360545SodiumHCID 113327931-(Pyridin-4-yl)piperidin-4-oneHCID 22727156Benzyl 4-amino-3-oxopiperazine-1-carboxylate

Product 1

HCID 178254544-Benzyloxycarbonyl-1-[1-(4-pyridyl)-4-piperidinylamino]-2-piperazinoneYield 70.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 1-amino-4-benzyloxycarbonyl-2-piperazinone (21.92 g) and 1-(4-pyridyl)-4-piperidone (15.51 g) in ethanol (500 ml) was dehydrated using a Soxlet extractor packed with molecular sieves 4A while refluxing for 24 hours. The reaction mixture was concentrated to obtain a residue, which was dissolved in methanol (300 ml) and combined with acetic acid (18.26 g) with cooling on ice followed by sodium cycanoborohydride (7.16 g) and then stirred at 0° C. for 3 hours. The reaction mixture was concentrated, and the residue was combined with a 1N aqueous solution of sodium hydroxide, and extracted with methylene chloride. The extract was washed with water and brine, dried and concentrated to obtain 4-benzyloxycarbonyl-1-[1-(4-pyridyl)-4-piperidinylamino]-2-piperazinone (25.29 g) as a pale yellow amorphous material.

Workup

  1. temperaturewhile refluxing for 24 hours
  2. concentrationThe reaction mixture was concentrated
  3. customto obtain a residue, which
  4. temperaturewith cooling on ice
  5. concentrationThe reaction mixture was concentrated
  6. extractionextracted with methylene chloride
  7. washThe extract was washed with water and brine
  8. customdried
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-75179fc5facb4f8ea50aa3e0bad61c1a
Source dataset
uspto-grants-2004_04
Patent number
US06723722B1

Reaction notes

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