Sodium hydride → 4-(2-Methoxy-ethoxy)-1-(3-methoxy-4-nitro-phenyl)-piperidine

HRID 2382655Notes

Reaction equation

HRID 2382655 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:12]2[CH2:17][CH2:16][CH:15]([OH:18])[CH2:14][CH2:13]2)[CH:6]=[CH:7][C:8]=1[N+:9]([O-:11])=[O:10].[H-].[Na+].[CH3:21][O:22][CH2:23][CH2:24]Br.[Cl-].[NH4+]>CN(C)C=O.O>[CH3:21][O:22][CH2:23][CH2:24][O:18][CH:15]1[CH2:16][CH2:17][N:12]([C:5]2[CH:6]=[CH:7][C:8]([N+:9]([O-:11])=[O:10])=[C:3]([O:2][CH3:1])[CH:4]=2)[CH2:13][CH2:14]1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 809722-Bromoethyl methyl etherHCID 259188601-(3-Methoxy-4-nitrophenyl)piperidin-4-ol

Product 1

HCID 587485624-(2-Methoxy-ethoxy)-1-(3-methoxy-4-nitro-phenyl)-piperidineYield 29.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(3-Methoxy-4-nitro-phenyl)-piperidin-4-ol (300 mg, 1.2 mmol) in N,N-dimethylformamide (3.0 mL), sodium hydride (1.52 g, 3.8 mmol) is added. After stirring, 2-bromoethyl methyl ether (150 μl, 1.6 mmol) is added and the mixture is further stirred at 70° C. for 15 hours. After addition of saturated aqueous ammonium chloride, the mixture is poured into water and extracted twice with ethyl acetate. The organic layer is washed with brine, dried over sodium sulfate, and evaporated in vacuo. The residue is purified by silica gel column chromatography (n-hexane-ethyl acetate gradient) to afford 4-(2-Methoxy-ethoxy)-1-(3-methoxy-4-nitro-phenyl)-piperidine (111 mg, 29%) as a yellow oil.

Workup

  1. stirringthe mixture is further stirred at 70° C. for 15 hours
  2. extractionextracted twice with ethyl acetate
  3. washThe organic layer is washed with brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated in vacuo
  6. customThe residue is purified by silica gel column chromatography (n-hexane-ethyl acetate gradient)

Sources & evidence

ORD record
ord-2dca53d793254271a5301ef88675d999
Source dataset
uspto-grants-2012_09
Patent number
US08263590B2

Reaction notes

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