Phenyl isocyanate → tert-Butyl (3S)-3-{[4-(anilinocarbonyl)piperazin-1-yl]methyl}piperidine-1-carboxylate

HRID 603213Notes

Reaction equation

HRID 603213 reaction equation
[N:1]1([CH2:7][C@@H:8]2[CH2:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[C:21]1([N:27]=[C:28]=[O:29])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C1(C)C=CC=CC=1.CO>[NH:27]([C:28]([N:4]1[CH2:5][CH2:6][N:1]([CH2:7][C@@H:8]2[CH2:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]2)[CH2:2][CH2:3]1)=[O:29])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

5

Reactant 2

HCID 7672Phenyl isocyanateHCID 24886660tert-butyl (3S)-3-(piperazin-1-ylmethyl)piperidine-1-carboxylate

Product 1

HCID 57656784tert-Butyl (3S)-3-{[4-(anilinocarbonyl)piperazin-1-yl]methyl}piperidine-1-carboxylateYield 80.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent

Procedure

tert-Butyl (3S)-3-(piperazin-1-ylmethyl)piperidine-1-carboxylate (3.5 g) and phenyl isocyanate (1.62 g) were stirred in toluene (50 ml) at room temperature for 20 h. The solvent was then concentrated in-vacuo to afford a white solid. The solid was dissolved in methanol and passed through an SCX2 column. The SCX2 column was then flushed with 5% ammonia in methanol solution. The solution was collected and the solvent removed under reduced pressure. The resultant solid was re-crystallised from EtOAc and isoHexane, to afford the desired product as a white solid (4 g).

Workup

  1. concentrationThe solvent was then concentrated in-vacuo
  2. customto afford a white solid
  3. customThe SCX2 column was then flushed with 5% ammonia in methanol solution
  4. customThe solution was collected
  5. customthe solvent removed under reduced pressure
  6. customThe resultant solid was re-crystallised from EtOAc and isoHexane

Sources & evidence

ORD record
ord-96cc74bb4ac841f29741e3320a9951cf
Source dataset
uspto-grants-2011_03
Patent number
US07906645B2

Reaction notes

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