Diisopropylethylamine → 4-[(2-Chloro-5-nitro-pyridin-4-ylamino)-methyl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 2376706Notes

Reaction equation

HRID 2376706 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](Cl)[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1.C(N(C(C)C)CC)(C)C.[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][CH:31]([CH2:34][NH2:35])[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22]>CCO.CC(N(C)C)=O>[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][CH:31]([CH2:34][NH:35][C:6]2[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=[C:2]([Cl:1])[CH:7]=2)[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 7368171-Boc-4-(aminomethyl)piperidineHCID 122757652,4-Dichloro-5-nitropyridine

Product 1

HCID 587126834-[(2-Chloro-5-nitro-pyridin-4-ylamino)-methyl]-piperidine-1-carboxylic acid tert-butyl esterYield 81.2%

Reagents, catalysts & solvents 1

HCID 19970948EtOH DMASolvent

Procedure

2,4-Dichloro-5-nitro-pyridine (500 mg, 2.59 mmol) was dissolved in EtOH-DMA (15 mL, 1:1). To this solution was added diisopropylethyl amine (0.99 mL, 5.7 mmol) followed by 4-aminomethyl-piperidine-1-carboxylic acid tert-butyl ester (611 mg, 2.85 mmol). The reaction was stirred for 18 h, then concentrated in vacuo. The crude residue was rediluted in EtOAc and poured into H2O. The aqueous phase was separated and extracted two more times with EtOAc. The organic layers were combined, dried (Na2SO4), decanted and concentrated. The crude residue was purified by SiO2 flash chromatography eluting with 2% CH3OH—CH2Cl2 to afford 4-[(2-chloro-5-nitro-pyridin-4-ylamino)-methyl]-piperidine-1-carboxylic acid tert-butyl ester as a yellow foam (780 mg, 81%).

Workup

  1. concentrationconcentrated in vacuo
  2. additionThe crude residue was rediluted in EtOAc
  3. additionpoured into H2O
  4. customThe aqueous phase was separated
  5. extractionextracted two more times with EtOAc
  6. dry with materialdried (Na2SO4)
  7. customdecanted
  8. concentrationconcentrated
  9. customThe crude residue was purified by SiO2 flash chromatography
  10. washeluting with 2% CH3OH—CH2Cl2

Sources & evidence

ORD record
ord-026e4b9bc66840a7a8f6115eb04fc577
Source dataset
uspto-grants-2008_12
Patent number
US07468382B2

Reaction notes

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