4-Aminophenol → 4-[3-(4-Methylpiperazin-1-yl)propoxy]aniline

HRID 1038717Notes

Reaction equation

HRID 1038717 reaction equation
Cl.Cl[CH2:3][CH2:4][CH2:5][N:6]1[CH2:11][CH2:10][N:9]([CH3:12])[CH2:8][CH2:7]1.[NH2:13][C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1.[OH-].[Na+]>CN(C=O)C>[CH3:12][N:9]1[CH2:10][CH2:11][N:6]([CH2:5][CH2:4][CH2:3][O:20][C:17]2[CH:18]=[CH:19][C:14]([NH2:13])=[CH:15][CH:16]=2)[CH2:7][CH2:8]1

Participants

5

Reactant 3

HCID 4034-AminophenolHCID 14798Sodium HydroxideHCID 121960331-(3-Chloropropyl)-4-methylpiperazine hydrochloride

Product 1

HCID 221246044-[3-(4-Methylpiperazin-1-yl)propoxy]anilineYield 93.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-(3-Chloro-propyl)-4-methyl-piperazine hydrochloride (1.7 g, 9.6 mmol, 1.2 eq.) is added in one portion to a mixture of 4-aminophenol (893 mg, 8.0 mmol) and finely powdered sodium hydroxide (808 mg, 20 mmol, 2.5 eq.) in DMF (27 ml). The reaction mixture is stirred for 17 h at RT. The resulting dark suspension is filtered. The filtrate is diluted with DCM (200 ml) and washed with brine (2×50 ml). The aqueous layer is back-extracted with DCM. The organic phase is dried (sodium sulfate), filtered and concentrated. Purification of the residue by silica gel column chromatography (DCM/MeOH, 7:3) provides 1.86 g of the title compound as a yellow-brown oil: ESI-MS: 250.2 [MH]+; TLC: Rf=0.31 (DCM/MeOH, 7:3).

Workup

  1. filtrationThe resulting dark suspension is filtered
  2. additionThe filtrate is diluted with DCM (200 ml)
  3. washwashed with brine (2×50 ml)
  4. extractionThe aqueous layer is back-extracted with DCM
  5. dry with materialThe organic phase is dried (sodium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the residue by silica gel column chromatography (DCM/MeOH, 7:3)

Sources & evidence

ORD record
ord-af5081e1bfc547bb9fe336ed8309b06a
Source dataset
uspto-grants-2013_10
Patent number
US08552002B2

Reaction notes

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