Sodium Hydroxide → 4-[3-[[2-[4-(4,6-Dimethyl-2-pyridyl)piperazin-1-yl]-5-nitro-phenyl]methoxy]propyl]morpholine

HRID 880474Notes

Reaction equation

HRID 880474 reaction equation
[OH-].[Na+].[CH3:3][C:4]1[CH:9]=[C:8]([CH3:10])[N:7]=[C:6]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][C:18]=3[CH2:26][OH:27])[CH2:13][CH2:12]2)[CH:5]=1.Cl[CH2:29][CH2:30][CH2:31][N:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[CH3:3][C:4]1[CH:9]=[C:8]([CH3:10])[N:7]=[C:6]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][C:18]=3[CH2:26][O:27][CH2:29][CH2:30][CH2:31][N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)[CH2:13][CH2:12]2)[CH:5]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 958344-(3-Chloropropyl)morpholineHCID 66851343[2-[4-(4,6-Dimethyl-2-pyridyl)piperazin-1-yl]-5-nitro-phenyl]methanol

Product 1

HCID 668515124-[3-[[2-[4-(4,6-Dimethyl-2-pyridyl)piperazin-1-yl]-5-nitro-phenyl]methoxy]propyl]morpholineYield 80.2%

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 1140TolueneSolvent

Procedure

Aqueous sodium hydroxide (50% w/w, 10 g, 125 mmol) and tetrabutylammonium hydrogen sulfate (0.20 g) were added successively to a solution of [2-[4-(4,6-dimethyl-2-pyridyl)piperazin-1-yl]-5-nitro-phenyl]methanol (0.50 g, 1.46 mmol) in toluene (5 mL). The mixture was heated to reflux with vigorous stirring for 45 min then 4-(3-chloro-propyl)-morpholine (0.50 g, 3.00 mmol) was added and reflux continued for 28 h. The reaction mixture was cooled and the organic phase separated. The aqueous phase was extracted with ethyl acetate (3×5 mL). The organic phases were combined, washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to give a residue which was purified by preparative TLC eluting with 2% methanol in chloroform to afford 4-[3-[[2-[4-(4,6-dimethyl-2-pyridyl)piperazin-1-yl]-5-nitro-phenyl]methoxy]propyl]morpholine (550 mg, 80%) as a solid.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux
  3. temperaturereflux
  4. waitcontinued for 28 h
  5. temperatureThe reaction mixture was cooled
  6. customthe organic phase separated
  7. extractionThe aqueous phase was extracted with ethyl acetate (3×5 mL)
  8. washwashed with water and brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under vacuum
  12. customto give a residue which
  13. customwas purified by preparative TLC
  14. washeluting with 2% methanol in chloroform

Sources & evidence

ORD record
ord-faeaf4ac3ad04228bd9d382a74f3e674
Source dataset
uspto-grants-2015_03
Patent number
US08993574B2

Reaction notes

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