1-Phenylpiperazine → HCID 42633098, compound

HRID 417987Notes

Reaction equation

HRID 417987 reaction equation
[CH2:1]1[NH:6][CH2:5][CH2:4][N:3]([CH2:7]CCO)[CH2:2]1.CCN(C(C)C)C(C)C.Cl[C:21]([O:23][C:24]1[CH:29]=[CH:28]C([N+]([O-])=O)=CC=1)=[O:22].[CH:33]1[CH:34]=[CH:35][C:36]([N:39]2[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]2)=[CH:37][CH:38]=1>C(Cl)Cl>[C:36]1([N:39]2[CH2:40][CH2:41][N:42]([C:21]([O:23][CH2:24][CH2:29][CH2:28][N:6]3[CH2:5][CH2:4][N:3]([CH3:7])[CH2:2][CH2:1]3)=[O:22])[CH2:43][CH2:44]2)[CH:35]=[CH:34][CH:33]=[CH:38][CH:37]=1

Participants

6

Reactant 4

HCID 70961-PhenylpiperazineHCID 79207Piperazin-1-ylpropanolHCID 81531DiisopropylethylamineHCID 821294-Nitrophenyl chloroformate

Product 1

HCID 42633098HCID 42633098, compoundYield 11%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

1-(3-Hydroxypropyl)-4-piperazine (0.63 g, 4.0 mmol) was dissolved in DCM (30 mL) and cooled to 0° C. DIPEA (1.39 mL, 8.0 mmol) and p-nitrophenyl chloroformate (0.80 g, 4.0 mmol) were added. The reaction mixture was stirred at room temperature for 2 hours and then phenylpiperazine (0.61 mL, 4.0 mmol) was added. The reaction mixture was stirred at room temperature for 16 hours and then concentrated in vacuo. The residue was dissolved in EtOAc (100 mL) and washed sequentially with 1M aq Na2CO3 solution (4×100 mL), and concentrated in vacuo. The residue was purified by reverse phase chromatography (gradient eluting with MeOH in water, with 1% formic acid in each solvent, 0-30%). The resulting residue was dissolved in DCM (30 mL) and stirred with solid Na2CO3 for 20 minutes, filtered and concentrated in vacuo. The resulting residue was purified by reverse phase HPLC (gradient eluting with acetonitrile in water, 5-45%) to give 3-(4-methyl-piperazin-1-yl)propyl 4-phenylpiperazine-1-carboxylate (148 mg, 11%) as a colourless oil.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 16 hours
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in EtOAc (100 mL)
  4. washwashed sequentially with 1M aq Na2CO3 solution (4×100 mL)
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by reverse phase chromatography (gradient
  7. washeluting with MeOH in water, with 1% formic acid in each solvent, 0-30%)
  8. dissolutionThe resulting residue was dissolved in DCM (30 mL)
  9. stirringstirred with solid Na2CO3 for 20 minutes
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe resulting residue was purified by reverse phase HPLC (gradient eluting with acetonitrile in water, 5-45%)

Sources & evidence

ORD record
ord-98808eb8b0b8483cb9002618b28ded70
Source dataset
uspto-grants-2012_01
Patent number
US08093248B2

Reaction notes

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