Aniline → HCID 18700257, compound

HRID 2288731Notes

Reaction equation

HRID 2288731 reaction equation
[C:1]([CH:4]1[CH2:9][CH2:8][CH2:7][N:6]([C:10]([CH:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=3)[CH2:14][CH2:13]2)=[O:11])[CH2:5]1)([OH:3])=O.[NH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.OC1C2N=NNC=2C=CC=1.CN1CCOCC1>CCOCC>[C:25]1([NH:24][C:1]([CH:4]2[CH2:9][CH2:8][CH2:7][N:6]([C:10]([CH:12]3[CH2:17][CH2:16][N:15]([C:18]4[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=4)[CH2:14][CH2:13]3)=[O:11])[CH2:5]2)=[O:3])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

6

Reactant 4

HCID 6115AnilineHCID 79724-MethylmorpholineHCID 18700265HCID 18700265, compoundHCID 178418300HCID 178418300, compound

Product 1

HCID 18700257HCID 18700257, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
2.5 °C

Procedure

Dicyclocarbodiimide (620 mg) was added to a stirred mixture of the crude 3-carboxy-1-[4-pyridylpiperidin-4-ylcarbonyl]piperidine product from step (b) (1 g), aniline (0.17 ml), hydroxybenztriazole, (236 mg), N-methylmorpholine (0.29 ml) under an atmosphere of argon with cooling to 0 to 5° C. The mixture was stirred at 0° C. for 30 minutes and then allowed to warm to ambient temperature and stirred overnight. The mixture was quenched with water and the solvent removed by evaporation. The residue was partitioned between dichloromethane and water. The aqueous phase was seperated and washed with dichloromethane. The aqueous phase was evaporated and the residue purified by flash chromatography on silica gel using 15% MeOH/CHCl2 as eluent to give a crude product which was further purified by flash chromatography on silica gel using a gradient of 4 to 10% MeOH/CH2Cl2 as eluent to give an oil. Ether was added and then evaporated to yield 3-(phenylaminocarbonyl)-1-[1-(4-pyridyl)piperidin-4-ylcarbonyl]piperidine as a foam (200 mg; 80% pure);

Workup

  1. temperatureto warm to ambient temperature
  2. stirringstirred overnight
  3. customThe mixture was quenched with water
  4. customthe solvent removed by evaporation
  5. customThe residue was partitioned between dichloromethane and water
  6. customThe aqueous phase was seperated
  7. washwashed with dichloromethane
  8. customThe aqueous phase was evaporated
  9. customthe residue purified by flash chromatography on silica gel using 15% MeOH/CHCl2 as eluent
  10. customto give a crude product which
  11. customwas further purified by flash chromatography on silica gel using a gradient of 4 to 10% MeOH/CH2Cl2 as eluent
  12. customto give an oil
  13. customevaporated

Sources & evidence

ORD record
ord-085883cc87f9421ba8c42a8c766bb102
Source dataset
uspto-grants-2000_07
Patent number
US06090813

Reaction notes

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