Diisopropylethylamine → Tert-butyl 4-(6-nitropyridin-3-yl)piperazine-1-carboxylate

HRID 2359529Notes

Reaction equation

HRID 2359529 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([N+:8]([O-:10])=[O:9])=[N:6][CH:7]=1.[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].CCN(C(C)C)C(C)C>CC#N>[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][N:21]([C:2]2[CH:7]=[N:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=2)[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 8176205-Bromo-2-nitropyridine

Product 1

HCID 11243758Tert-butyl 4-(6-nitropyridin-3-yl)piperazine-1-carboxylateYield 80%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of 5-bromo-2-nitropyridine (4.93 g, 24.3 mmol) and piperazine-1-carboxylic acid tert-butyl ester (4.97 g, 26.7 mmol) in CH3CN (60 ml) is added DIPEA (4.65 mL, 26.7 mmol). The mixture is heated at reflux for 72 hours then cooled to room temperature and the precipitated product collected by filtration. The filtrate is concentrated and purified by flash column chromatography eluting with 30% EtOAc/petrol. The combined products are re-crystallized from EtOAc/petrol to give 4-(6-nitro-pyridin-3-yl)-piperazine-1-carboxylic acid tert-butyl ester, (4.50 g, 80% yield). MS (ESI) m/z 308 (M+H)+

Workup

  1. temperatureThe mixture is heated
  2. temperatureat reflux for 72 hours
  3. filtrationthe precipitated product collected by filtration
  4. concentrationThe filtrate is concentrated
  5. custompurified by flash column chromatography
  6. washeluting with 30% EtOAc/petrol
  7. customThe combined products are re-crystallized from EtOAc/petrol

Sources & evidence

ORD record
ord-c01bc490deb74968a1e8eb2642ec416b
Source dataset
uspto-grants-2014_04
Patent number
US08685980B2

Reaction notes

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