Thionyl Chloride → 1-Methyl-4-{2-[(4-methylpiperazin-1-yl)methyl]-4-nitrophenyl}piperazine

HRID 1190864Notes

Reaction equation

HRID 1190864 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][C:9]=2[CH2:17]O)[CH2:4][CH2:3]1.S(Cl)(Cl)=O.[CH3:23][N:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1>C1COCC1>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][C:9]=2[CH2:17][N:27]2[CH2:28][CH2:29][N:24]([CH3:23])[CH2:25][CH2:26]2)[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 531671-MethylpiperazineHCID 25918812[2-(4-Methylpiperazino)-5-nitrophenyl]methanol

Product 1

HCID 672468861-Methyl-4-{2-[(4-methylpiperazin-1-yl)methyl]-4-nitrophenyl}piperazineYield 92%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To [2-(4-methylpiperazin-1-yl)-5-nitrophenyl]methanol (0.150 g, 0.60 mmol) in 5 mL of THF at 0° C. was added thionyl chloride (0.22 mL, 5 eq). The reaction mixture was refluxed for 45 minutes and then the solvent and the excess of thionyl chloride were evaporated. The residue was suspended in 5 mL of acetonitrile and 1-methylpiperazine (0.33 mL, 5 eq) was added at 0° C. The solution was stirred overnight at room temperature, evaporated and the residue was dissolved in ethyl acetate and washed with a saturated aqueous solution of Na2CO3. The aqueous layer was extracted with ethyl acetate and then the combined organic layers were dried over Na2SO4, filtered and evaporated. The residue was thoroughly washed with pentane and filtered off to yield expected compound as an orange powder (0.185 g, 92% yield).

Workup

  1. temperatureThe reaction mixture was refluxed for 45 minutes
  2. customthe solvent and the excess of thionyl chloride were evaporated
  3. customevaporated
  4. dissolutionthe residue was dissolved in ethyl acetate
  5. washwashed with a saturated aqueous solution of Na2CO3
  6. extractionThe aqueous layer was extracted with ethyl acetate
  7. dry with materialthe combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. washThe residue was thoroughly washed with pentane
  11. filtrationfiltered off

Sources & evidence

ORD record
ord-5fe87e2c3bd847518b8283cbdb52eb14
Source dataset
uspto-grants-2014_03
Patent number
US08680095B2

Reaction notes

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