Hydrogen Peroxide → 1,1-Dimethylethyl 4-{[2-(aminocarbonyl)phenyl]amino}-1-piperidinecarboxylate

HRID 883775Notes

Reaction equation

HRID 883775 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[NH:9][CH:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]1)#[N:2].[OH-:23].[Na+].OO>CCO.O.[Na+].[Cl-]>[NH2:2][C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[NH:9][CH:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]1)=[O:23]

Participants

7

Reactant 3

HCID 784Hydrogen Peroxide3×HCID 14798Sodium HydroxideHCID 576995121,1-Dimethylethyl 4-[(2-cyanophenyl)amino]-1-piperidinecarboxylate

Product 1

HCID 576995251,1-Dimethylethyl 4-{[2-(aminocarbonyl)phenyl]amino}-1-piperidinecarboxylate

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolvent3×HCID 5234Sodium ChlorideSolvent

Procedure

To a solution of 1,1-dimethylethyl 4-[(2-cyanophenyl)amino]-1-piperidinecarboxylate (D17) (355 mg, 1.18 mmol) in EtOH (6 ml) at 40° C. was added 2M NaOH solution (2.6 ml) followed by a mixture of hydrogen peroxide solution (27% w/w, 3.7 ml) in water (2.9 ml) and the reaction stirred for 2 h. Further hydrogen peroxide solution (27% w/w, 3.7 ml) in water (2.9 ml) was added and the reaction stirred at 40° C. for 1.5 h. Another portion of hydrogen peroxide solution (27% w/w, 7.4 ml) in water (5.8 ml) was added and stirring and heating were continued overnight. The reaction mixture was diluted with saturated aqueous NaCl solution (4 ml) and extracted with tBuOH (5 ml). The organic extract was diluted with EtOAc (15 ml), dried (MgSO4) and concentrated. Column chromatography eluting with 0-100% EtOAc/petroleum ether gave the title compound (150 mg). δH (CDCl3, 250 MHz) 7.96 (1H, br d), 7.40 (1H, m), 7.31 (1H, m), 6.71 (1H, d), 6.57 (1H, t), 5.80 (2H, br s), 3.93 (2H, m), 3.53 (1H, m), 3.06 (2H, m), 1.99 (2H, m), 1.50 (2H, m), 1.47 (9H, s). MS (ES): MH+ 320.

Workup

  1. stirringthe reaction stirred at 40° C. for 1.5 h
  2. stirringstirring
  3. temperatureheating
  4. waitwere continued overnight
  5. extractionextracted with tBuOH (5 ml)
  6. extractionThe organic extract
  7. additionwas diluted with EtOAc (15 ml)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. washColumn chromatography eluting with 0-100% EtOAc/petroleum ether

Sources & evidence

ORD record
ord-e864ea9cb252448599776286c0c24d17
Source dataset
uspto-grants-2012_08
Patent number
US08236953B2

Reaction notes

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