Nitrogen mustard hydrochloride → 1-Methyl4-(3-nitro-4-piperidin-1-yl-phenyl)-piperazine

HRID 646851Notes

Reaction equation

HRID 646851 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([NH2:16])[CH:7]=[CH:8][C:9]=1[N:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1)([O-:3])=[O:2].[CH3:17][N:18]([CH2:22][CH2:23]Cl)[CH2:19][CH2:20]Cl.Cl.C([O-])([O-])=O.[K+].[K+]>CCO>[CH3:17][N:18]1[CH2:22][CH2:23][N:16]([C:6]2[CH:7]=[CH:8][C:9]([N:10]3[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]3)=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)[CH2:20][CH2:19]1

Participants

5

Reactant 3

HCID 5935Nitrogen mustard hydrochlorideHCID 11430Potassium CarbonateHCID 27602373-Nitro-4-(piperidin-1-yl)aniline

Product 1

HCID 586384911-Methyl4-(3-nitro-4-piperidin-1-yl-phenyl)-piperazineYield 71.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 512 mg g (2.31 mmol) of 3-nitro-4-piperidin-1-yl-phenylamine (as prepared in the previous step) and 404 mg (2.10 mmol) of mechlorethamine hydrochloride in 15 mL of EtOH was added 1.45 g (10.5 mmol) of anh K2CO3 and the mixture heated to reflux under Ar for 48 h. The mixture was cooled to RT, concentrated in vacuo, extracted with EtOAc (3×20 mL) and the combined extracts filtered (Celite), and concentrated to a dark oil. Chromatography of the resulting residue on a 70-g silica SPE column with a gradient of 0-3% MeOH-dichloromethane afforded 456 mg (71%) of the title compound as a dark red solid: Mass spectrum (ESI, m/z): Calcd. for C16H24N4O2, 305.2 (M+H), found 305.1.

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux under Ar for 48 h
  3. concentrationconcentrated in vacuo
  4. extractionextracted with EtOAc (3×20 mL)
  5. filtrationthe combined extracts filtered (Celite)
  6. concentrationconcentrated to a dark oil

Sources & evidence

ORD record
ord-af2970f9b32845f3a8b956e924c0a2aa
Source dataset
uspto-grants-2010_04
Patent number
US07705042B2

Reaction notes

Loading…