Triethylamine → Tert-butyl 3-((2-bromo-5-nitropyridin-4-yl)amino)piperidine-1-carboxylate

HRID 919643Notes

Reaction equation

HRID 919643 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.[Br:15][C:16]1[CH:21]=[C:20](Br)[C:19]([N+:23]([O-:25])=[O:24])=[CH:18][N:17]=1.CCN(CC)CC.[OH-].[Na+]>CCO.CCOC(C)=O>[Br:15][C:16]1[CH:21]=[C:20]([NH:1][CH:2]2[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]2)[C:19]([N+:23]([O-:25])=[O:24])=[CH:18][N:17]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 5458091-BOC-3-AminopiperidineHCID 160998502,4-Dibromo-5-nitropyridine

Product 1

HCID 86706484Tert-butyl 3-((2-bromo-5-nitropyridin-4-yl)amino)piperidine-1-carboxylateYield 43.3%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

The tert-butyl 3-aminopiperidine-1-carboxylate (1.43 g, 7.14 mmol, 1.0 eq) was added dropwise to a solution of 2,4-dibromo-5-nitropyridine (2 g, 7.14 mmol, 1.0 eq) and Et3N (0.73 g, 7.14 mmol, 1.0 eq) in EtOH (20 mL) at reflux temperature. The reaction mixture was heated at refluxing for 16 h and then the solvent was concentrated in vacuo to afford a residue. The residue was treated with 1 N NaOH solution and extraction with EtOAc. The organic phase was separated, dried (Na2SO4) and concentration in vacuo to afford an residue which was purified by silica gel column chromatography with EtOAc in PE (⅕ v/v) to give the title compound (1.24 g, 42%) as yellow solid. 1H NMR (400 MHz, CDCl3) δ: 8.99 (s, 1H), 8.25 (s, 1H), 6.98 (s, 1H), 3.81-3.79 (m, 1H), 3.61-3.60 (m, 2H), 3.37-3.35 (m, 2H), 2.02 (m, 1H), 1.86-1.77 (m, 3H), 1.47 (s, 9H). ESI-MS (M+H+): 401.0.

Workup

  1. temperatureat reflux temperature
  2. temperatureThe reaction mixture was heated
  3. temperatureat refluxing for 16 h
  4. concentrationthe solvent was concentrated in vacuo
  5. customto afford a residue
  6. customThe organic phase was separated
  7. customdried
  8. concentration(Na2SO4) and concentration in vacuo
  9. customto afford an residue which
  10. customwas purified by silica gel column chromatography with EtOAc in PE (⅕ v/v)

Sources & evidence

ORD record
ord-4890278b8bc34944a8e2ba54c2ce8c3e
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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