1-(2-Methoxyphenyl)piperazine → 1-(2-Methoxyphenyl)-4-methylpiperazine

HRID 429134Notes

Reaction equation

HRID 429134 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH3:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[N:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1.[CH:21](OCC)=O.[OH-].[Na+]>O1CCCC1.O>[CH3:21][N:18]1[CH2:19][CH2:20][N:15]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[O:8][CH3:7])[CH2:16][CH2:17]1

Participants

7

Reactant 4

HCID 13461-(2-Methoxyphenyl)piperazineHCID 8025Ethyl formateHCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydride

Product 1

HCID 98591201-(2-Methoxyphenyl)-4-methylpiperazineYield 53.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To an ice-cooled, stirred suspension of lithium aluminium hydride (7.9 g, 0.21 mol) in dry tetrahydrofuran (1 50 ml) was added a solution of 1-(2-methoxyphenyl) piperazine (10 g, 52 mmol) in dry tetrahydrofuran (150 ml) over 0.5 h under argon. A solution of ethyl formate (12.6 ml, 0.156 mol) in dry tetrahydrofuran (25 ml) was added to the cold mixture over 0.25 h and the resulting suspension was stirred for a further 2 h at room temperature. Dilute sodium hydroxide solution (15%, 8 ml) was slowly added to the cooled mixture, followed by water (24 ml) and the whole left to stir for 0.25 h. The mixture was filtered and the filtrate concentrated to an oil which was partitioned between dichloromethane and water. The organic phase was dried and concentrated to an oil which was purified by column chromatography on silica gel eluting with a methanol/dichloromethane gradient to afford the title compound as a colourless oil (5.7 g, 53%)

Workup

  1. stirringthe resulting suspension was stirred for a further 2 h at room temperature
  2. waitthe whole left
  3. stirringto stir for 0.25 h
  4. filtrationThe mixture was filtered
  5. concentrationthe filtrate concentrated to an oil which
  6. customwas partitioned between dichloromethane and water
  7. customThe organic phase was dried
  8. concentrationconcentrated to an oil which
  9. customwas purified by column chromatography on silica gel eluting with a methanol/dichloromethane gradient

Sources & evidence

ORD record
ord-c181bbeacf3547c3ba1cb2880c3bd3dd
Source dataset
uspto-grants-2001_11
Patent number
US06316450B1

Reaction notes

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