Triethylamine → tert-Butyl 4-(5-nitropyridin-2-yl)piperazine-1-carboxylate

HRID 1993636Notes

Reaction equation

HRID 1993636 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=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].C(N(CC)CC)C.C(OCC)(=O)C>C(O)CCC.O>[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][N:21]([C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=2)[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 783082-Chloro-5-nitropyridineHCID 143452tert-Butyl piperazine-1-carboxylate

Product 1

HCID 16217943tert-Butyl 4-(5-nitropyridin-2-yl)piperazine-1-carboxylateYield 58.6%

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

Place 2-chloro-5-nitro-pyridine (1.0 g, 6.31 mmol), piperazine-1-carboxylic acid tert-butyl ester (1.76 g, 9.45 mmol), and triethylamine (1.76 mL, 12.6 mmol) in n-butanol (20 mL). Heat to 120° C. for 17 hours. Cool to room temperature and add ethyl acetate and water. Separate organic layer and wash with water and saturated aq. sodium chloride. Collect organic layer, dry over Mg2SO4, filter, and concentrate under reduced pressure. Subject residue to silica gel chromatography eluting with 20% EtOAc:hexane to yield 1.14 g (58%) of 4-(5-nitro-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester. MS(ES): m/z=309 [M+H].

Workup

  1. temperatureCool to room temperature
  2. washSeparate organic layer and wash with water and saturated aq. sodium chloride
  3. dry with materialCollect organic layer, dry over Mg2SO4
  4. filtrationfilter
  5. concentrationconcentrate under reduced pressure
  6. washSubject residue to silica gel chromatography eluting with 20% EtOAc

Sources & evidence

ORD record
ord-17e283a86527489cbcce5797e5e2a978
Source dataset
uspto-grants-2010_01
Patent number
US07652015B2

Reaction notes

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