Sodium hydride → 1-(4-Pyridyl)-3-(5-nitro-2-pyridyloxy)pyrrolidine

HRID 346681

Reaction equation

HRID 346681 reaction equation
[H-].[Na+].[N:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10]2)=[CH:5][CH:4]=1.Br[C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][N:17]=1>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[N:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:13][CH2:12][CH:11]([O:14][C:16]3[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][N:17]=3)[CH2:10]2)=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 782402-Bromo-5-nitropyridineHCID 219061981-(Pyridin-4-yl)pyrrolidin-3-ol

Product 1

HCID 183571081-(4-Pyridyl)-3-(5-nitro-2-pyridyloxy)pyrrolidine

Reagents, catalysts & solvents 1

HCID 74236Tetrabutylammonium BromideCatalyst

Procedure

Sodium hydride (60% dispersion in paraffin oil, 146 mg) 1.2 equivalent) was added to an oven-dried round-bottomed flask and washed under an argon atmosphere with pentane. DMF (5 ml) was then added, followed by 1-(4-pyridyl)-3-hydroxypyrrolidine (1.0 equivalent, 3.05 mmol) and tetra-n-butylammonium bromide (59 mg, 0.18 mmol). The mixture was added as a slurry to 2-bromo-5-nitropyridine (1.5 equivalent) in a second dry flask under argon, with stirring. After the reaction was complete the solvent was evaporated under vacuum. The residue was purified by chromatography on silica, eluting from 1%MeOH/1%NH4OH/CH2Cl2 to 10%MeOH/1%NH4OH/CH2Cl2 (in 1% increments). The crude product was recrystallised from EtOAc to give 1-(4-pyridyl)-3-(5-nitro-2-pyridyloxy)pyrrolidine as a pale brown solid (460 mg);

Workup

  1. washwashed under an argon atmosphere with pentane
  2. additionDMF (5 ml) was then added
  3. customwas evaporated under vacuum
  4. customThe residue was purified by chromatography on silica
  5. washeluting from 1%MeOH/1%NH4OH/CH2Cl2 to 10%MeOH/1%NH4OH/CH2Cl2 (in 1% increments)
  6. customThe crude product was recrystallised from EtOAc

Sources & evidence

ORD record
ord-5f82f0d21b16461baaf51b1e0584d208
Source dataset
uspto-grants-2007_02
Patent number
US07173025B1

Linked notes

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