2-Chloro-3-nitropyridine → N-(1-benzylpiperidin-4-yl)-3-nitropyridin-2-amine

HRID 1068167Notes

Reaction equation

HRID 1068167 reaction equation
Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[CH2:11]([N:18]1[CH2:23][CH2:22][CH:21]([NH2:24])[CH2:20][CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(C(C)C)CC)(C)C>C1COCC1.CCOC(C)=O>[CH2:11]([N:18]1[CH2:23][CH2:22][CH:21]([NH:24][C:2]2[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=2)[CH2:20][CH2:19]1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

6

Reactant 3

HCID 796132-Chloro-3-nitropyridineHCID 81531DiisopropylethylamineHCID 4158521-Benzyl-4-piperidylamine

Product 1

HCID 2823254N-(1-benzylpiperidin-4-yl)-3-nitropyridin-2-amineYield 36.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1.64 g 2-chloro-3-nitropyridine and 1.37 g of 1-benzyl-piperidin-4-ylamine in 20 mL THF was added diisopropylethylamine. The reaction was refluxed for 6 hours. The reaction was cooled down, diluted with 50 mL of EtOAc and washed with 30 mL of saturated NaHCO3 aqueous solution. After separating layers, the aqueous phase was extracted with 2×30 mL of EtOAc. The combined organic phases were washed with 15 mL of brine, dried over MgSO4 and concentrated under reduced pressure. The residue was purified by flash chromatography eluting with 25% EtOAc in hexane, then 50% EtOAc in hexane and 100% EtOAc to give 823 mg of the title compound as a yellow solid.

Workup

  1. temperatureThe reaction was refluxed for 6 hours
  2. temperatureThe reaction was cooled down
  3. washwashed with 30 mL of saturated NaHCO3 aqueous solution
  4. customAfter separating layers
  5. extractionthe aqueous phase was extracted with 2×30 mL of EtOAc
  6. washThe combined organic phases were washed with 15 mL of brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography
  10. washeluting with 25% EtOAc in hexane

Sources & evidence

ORD record
ord-6cf68fff0d7d42fea6a2dd5ba87ab984
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

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