Cyclobutanone → Tert-butyl 4-(4-(1-cyanocyclobutylamino)phenyl)piperazine-1-carboxylate

HRID 245002Notes

Reaction equation

HRID 245002 reaction equation
C[Si]([C:5]#[N:6])(C)C.[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][N:17]([C:20]2[CH:25]=[CH:24][C:23]([NH2:26])=[CH:22][CH:21]=2)[CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].[C:27]1(=O)[CH2:30][CH2:29][CH2:28]1.S([O-])([O-])(=O)=O.[Na+].[Na+]>ClCCl.CC(C)=O>[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][N:17]([C:20]2[CH:21]=[CH:22][C:23]([NH:26][C:27]3([C:5]#[N:6])[CH2:30][CH2:29][CH2:28]3)=[CH:24][CH:25]=2)[CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:8])[CH3:9]

Participants

7

Reactant 4

HCID 14496CyclobutanoneHCID 24436Sodium SulfateHCID 82115Trimethylsilyl cyanideHCID 11011301tert-Butyl 4-(4-aminophenyl)piperazine-1-carboxylate

Product 1

HCID 67132054Tert-butyl 4-(4-(1-cyanocyclobutylamino)phenyl)piperazine-1-carboxylateYield 84%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 6344DichloromethaneSolvent2×

Procedure

Trimethylsilyl cyanide (0.3 g, 3 mmol) was added dropwise to a mixture of 43a (0.415 g, 1.5 mmol), cyclobutanone (0.21 g, 3 mmol) and sodium sulfate (1 g) in dichloromethane (5 ml). The mixture was stirred for 15 hours. After filtration to eliminate sodium sulfate, the medium was concentrated under vacuum to obtain a brown liquid which was subjected to chromatography (dichloromethane:acetone, 75:25) to yield 43b (0.448 g, 1.26 mmol, 84%) as a yellow solid.

Workup

  1. filtrationAfter filtration
  2. concentrationthe medium was concentrated under vacuum
  3. customto obtain a brown liquid which

Sources & evidence

ORD record
ord-abcc370a781949648039819a9039462c
Source dataset
uspto-grants-2014_02
Patent number
US08658681B2

Reaction notes

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