Sodium Iodide → 1-[3-(2-Methoxy-5-nitrophenoxy)propyl]-4-methylpiperazine

HRID 1593785Notes

Reaction equation

HRID 1593785 reaction equation
Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[C:10]([N+:12]([O-:14])=[O:13])[CH:9]=[CH:8][C:7]=1[O:15][CH3:16].[I-].[Na+].[CH3:19][N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1>COCCOC>[CH3:16][O:15][C:7]1[CH:8]=[CH:9][C:10]([N+:12]([O-:14])=[O:13])=[CH:11][C:6]=1[O:5][CH2:4][CH2:3][CH2:2][N:23]1[CH2:24][CH2:25][N:20]([CH3:19])[CH2:21][CH2:22]1

Participants

5

Reactant 3

HCID 5238Sodium IodideHCID 531671-MethylpiperazineHCID 133001802-(3-Chloropropoxy)-1-methoxy-4-nitrobenzene

Product 1

HCID 468640581-[3-(2-Methoxy-5-nitrophenoxy)propyl]-4-methylpiperazine

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

2(3-chloropropoxy)-1-methoxy-4-nitrobenzene, (100 g, 0.407 mol) and sodium iodide (9.2 g, 0.614 mol) was added to 520 mL of dry 1,2-dimethoxyethane. To the mixture was then added N-methylpiperazine (82 g, 0.814 mol). Stirred and heated the reaction to reflux. The reaction was monitored by HPLC. After 8 hours, the heating mantle was removed and the reaction was allowed to cool to ambient temperature. The reaction mixture was then drowned in 1 L of ethyl acetate and stirred for a minimum of 1 hour. Bright yellow solids precipitated. The mixture was filtered and rinsed and the salts collected with ethyl acetate. The filtrate was washed once with 400 mL of 0.5 N NaOH. The layers were separated and the organic layer was washed with water (3×390 mL). The combined organic layers were concentrated under vacuum at 35-40° C. to obtain 97.8 g (light orange oil) (77%); 1H NMR (300 MHz, CDCl3) δ 7.91 (dd, J=2.6, 9 Hz, 1H), 7.77 (d, J=2.6 Hz, 1H), 6.90 (d, J=9 Hz, 1H), 4.14 (t, J=7 Hz, 2H), 3.96 (s, 3H) 2.54 (t, J=7 Hz, 2H), 2.48 (m, 8H), 2.30 (s, 3H), 2.06 (m, 2H); MS (ES) m/z310.1 (M+H).

Workup

  1. temperatureheated
  2. customthe reaction
  3. temperatureto reflux
  4. customthe heating mantle was removed
  5. stirringstirred for a minimum of 1 hour
  6. customBright yellow solids precipitated
  7. filtrationThe mixture was filtered
  8. washrinsed
  9. customthe salts collected with ethyl acetate
  10. washThe filtrate was washed once with 400 mL of 0.5 N NaOH
  11. customThe layers were separated
  12. washthe organic layer was washed with water (3×390 mL)
  13. concentrationThe combined organic layers were concentrated under vacuum at 35-40° C.
  14. customto obtain 97.8 g (light orange oil) (77%)

Sources & evidence

ORD record
ord-b2ed9d704e0447eea51f194d22960441
Source dataset
uspto-grants-2007_11
Patent number
US07297795B2

Reaction notes

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