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

HRID 1962103Notes

Reaction equation

HRID 1962103 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/petrolto 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/

Sources & evidence

ORD record
ord-3a06cbfc12a741eb8ab7be7c8760d5a0
Source dataset
uspto-grants-2013_04
Patent number
US08415355B2

Reaction notes

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