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

HRID 1483047Notes

Reaction equation

HRID 1483047 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-d5d977b166854902ade5fc09130078d1
Source dataset
uspto-grants-2016_08
Patent number
US09416136B2

Reaction notes

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