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

HRID 384650Notes

Reaction equation

HRID 384650 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-e79c3115d16243d195c5839865ce5b99
Source dataset
uspto-grants-2013_02
Patent number
US08367658B2

Reaction notes

Loading…