Ammonium Chloride → 2-Benzoyl-1,4-bis(phenylmethyl)piperazine dihydrochloride

HRID 1713493Notes

Reaction equation

HRID 1713493 reaction equation
[C:1]1([CH2:7][N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:10][CH:9]2[C:21](N(OC)C)=[O:22])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:27]1([Mg]Br)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.[Cl-:35].[NH4+]>O1CCCC1>[ClH:35].[ClH:35].[C:21]([CH:9]1[CH2:10][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:12][CH2:13][N:8]1[CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)(=[O:22])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 231219081,4-Bis(phenylmethyl)-N-methoxy-N-methyl-2-piperazine carboxamideHCID 178418255HCID 178418255, compound

Product 1

HCID 231218302-Benzoyl-1,4-bis(phenylmethyl)piperazine dihydrochlorideYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

1,4-Bis(phenylmethyl)-N-methoxy-N-methyl-2-piperazine carboxamide (2.9 g, 8.1 mmol) was dissolved in tetrahydrofuran (30 mL) under argon atmosphere. A 1.0 M solution of phenylmagnesium bromide in tetrahydrofuran (24 mL, 24 mmol) was added dropwise thereto over 30 minutes with ice cooling. After the mixture was stirred at room temperature for 14 hours, an aqueous saturated ammonium chloride solution (200 mL) was added dropwise thereto with ice cooling, and the resulting mixture was extracted with ethyl acetate (200 ml). The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified with silica gel column chromatography (hexane to hexane:ethyl acetate=2:1). The fractions were collected and concentrated. The residue was dissolved in ethyl acetate, a 4 N hydrogen chloride/ethyl acetate solution (4 mL) was added thereto, and the resulting mixture was stirred at room temperature for 5 minutes. The resulting crystals were collected by filtration and washed with ethyl acetate to obtain the title compound (1.5 g, yield 51%).

Workup

  1. extractionwith ice cooling, and the resulting mixture was extracted with ethyl acetate (200 ml)
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified with silica gel column chromatography (hexane to hexane:ethyl acetate=2:1)
  6. customThe fractions were collected
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in ethyl acetate
  9. additiona 4 N hydrogen chloride/ethyl acetate solution (4 mL) was added
  10. stirringthe resulting mixture was stirred at room temperature for 5 minutes
  11. filtrationThe resulting crystals were collected by filtration
  12. washwashed with ethyl acetate

Sources & evidence

ORD record
ord-35d188bd0e4c4051bfe0bbec5725ef8e
Source dataset
uspto-grants-2010_09
Patent number
US07795267B2

Reaction notes

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