Methanol → [2-(4-Nitro-phenyl)-ethyl]-[2-(4-phenyl-piperazin-1-yl)-ethyl]-amine

HRID 1516785Notes

Reaction equation

HRID 1516785 reaction equation
[BH4-].[Na+].[N+:3]([C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C:13]([NH:15][CH2:16][CH2:17][N:18]2[CH2:23][CH2:22][N:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:20][CH2:19]2)=O)=[CH:8][CH:7]=1)([O-:5])=[O:4].CO>C1COCC1>[N+:3]([C:6]1[CH:11]=[CH:10][C:9]([CH2:12][CH2:13][NH:15][CH2:16][CH2:17][N:18]2[CH2:19][CH2:20][N:21]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH2:22][CH2:23]2)=[CH:8][CH:7]=1)([O-:5])=[O:4]

Participants

5

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 222613202-(4-nitrophenyl)-N-(2-(4-phenylpiperazin-1-yl)ethyl)acetamide

Product 1

HCID 22261321[2-(4-Nitro-phenyl)-ethyl]-[2-(4-phenyl-piperazin-1-yl)-ethyl]-amineYield 73%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of NaBH4 (0.449 g, 11.81 mmol) in 50 mL of dry THF at 0° C. under N2 was added dropwise 48% w/w BF3 ether complex (1.47 mL, 11.68 mmol). The cooling bath was removed and the solution was stirred for 1 h at room temperature. Into the above was added dropwise a solution of 2-(4-nitro-phenyl)-N-[2-(4-phenyl-piperazin-1-yl)-ethyl]-acetamide 26a (0.55 g, 1.49 mmol) dissolved in THF (5 mL). The reaction mixture was refluxed for 6 h. After the solution cooled to room temperature, methanol (5 mL) was added slowly. The solvent was removed under reduced pressure and 10% HCl/MeOH (25 mL) was added to the residue and the solution refluxed for 1 h. Solid NaHCO3 was added and methanol was removed in vacuo. The mixture was extracted with EtOAc. The combined organic phase was dried over Na2SO4 and evaporated to give the crude product which was purified by chromatography (EtOAc/MeOH=4/1) to give 27a: 0.385 g (73% yield) as a colorless oil. 1H NMR (CDCl3, 400 MHz): δ 1.62 (1H, bs, NH), 2.50 (2H, t, J=5.6 Hz, CH2—CH2NH), 2.58 (4H, t, J=4.8 Hz, (CH2)2N), 2.76 (2H, t, J=5.6 Hz, CH2Ar), 2.90-2.96 (4H, m, (CH2)2NH), 3.14 (4H, t, J=4.8 Hz, (CH2)2NPh), 6.85 (1H, t, J=7.2, ArH), 6.90 (2H, d, J=9.2, ArH), 7.25 (2H, t, J=9.2, ArH), 7.37 (2H, d, J=8.8, ArH), 8.15 (2H, d, J=8, ArH).

Workup

  1. customThe cooling bath was removed
  2. temperatureThe reaction mixture was refluxed for 6 h
  3. temperatureAfter the solution cooled to room temperature
  4. customThe solvent was removed under reduced pressure and 10% HCl/MeOH (25 mL)
  5. additionwas added to the residue
  6. temperaturethe solution refluxed for 1 h
  7. additionSolid NaHCO3 was added
  8. custommethanol was removed in vacuo
  9. extractionThe mixture was extracted with EtOAc
  10. dry with materialThe combined organic phase was dried over Na2SO4
  11. customevaporated
  12. customto give the crude product which
  13. customwas purified by chromatography (EtOAc/MeOH=4/1)

Sources & evidence

ORD record
ord-9201297a029e47f7a6a9be66953a3c80
Source dataset
uspto-grants-2012_07
Patent number
US08227604B2

Reaction notes

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