Dimethylformamide → Tert-butyl 4-((2-bromo-5-nitropyridin-4-yloxy)methyl)piperidine-1-carboxylate

HRID 556809Notes

Reaction equation

HRID 556809 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][OH:15])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[H-].[Na+].CN(C=O)C.[Br:23][C:24]1[CH:29]=[C:28](Cl)[C:27]([N+:31]([O-:33])=[O:32])=[CH:26][N:25]=1>CCOCC>[Br:23][C:24]1[CH:29]=[C:28]([O:15][CH2:14][CH:11]2[CH2:12][CH2:13][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:9][CH2:10]2)[C:27]([N+:31]([O-:33])=[O:32])=[CH:26][N:25]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylateHCID 596134182-Bromo-4-chloro-5-nitropyridine

Product 1

HCID 59613339Tert-butyl 4-((2-bromo-5-nitropyridin-4-yloxy)methyl)piperidine-1-carboxylateYield 62%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

N-Boc-4-piperidinemethanol (860 mg, 4.0 mmol) was added to a suspension of 60% sodium hydride (160 mg, 4.0 mmol) in DMF (40 mmol) at room temperature. After 20 minutes, 2-bromo-4-chloro-5-nitropyridine (949 mg, 4.0 mmol) was added in one portion, and the resulting mixture was stirred overnight at room temperature. The mixture was diluted with ether and washed with water. The aqueous phase was extracted with ether. The combined organic phases were washed with water and brine, then dried (Na2SO4) and concentrated. Silica column chromatography, eluting with 20% ethyl acetate-hexane, gave tert-butyl 4-((2-bromo-5-nitropyridin-4-yloxy)methyl)piperidine-1-carboxylate (789 mg, 62%) as a viscous, pale yellow oil which solidified on standing.

Workup

  1. washwashed with water
  2. extractionThe aqueous phase was extracted with ether
  3. washThe combined organic phases were washed with water and brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. washSilica column chromatography, eluting with 20% ethyl acetate-hexane

Sources & evidence

ORD record
ord-4a30ddc0d60348ce98b31eb6514361be
Source dataset
uspto-grants-2011_11
Patent number
US08058045B2

Reaction notes

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