3-Methylglutaric anhydride → 4-Methyl-1-[[3-[[1-[2-(1-methylethoxy)phenyl]-4-piperazinyl]methyl]phenyl]methyl]piperidine-2,6-dione

HRID 1034143Notes

Reaction equation

HRID 1034143 reaction equation
[CH3:1][CH:2]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:16][CH2:15][N:14]([CH2:17][C:18]2[CH:19]=[C:20]([CH:23]=[CH:24][CH:25]=2)[CH2:21][NH2:22])[CH2:13][CH2:12]1)[CH3:3].[CH3:26][CH:27]1[CH2:33][C:32](=O)[O:31][C:29](=[O:30])[CH2:28]1>C1COCC1>[CH3:26][CH:27]1[CH2:28][C:29](=[O:30])[N:22]([CH2:21][C:20]2[CH:23]=[CH:24][CH:25]=[C:18]([CH2:17][N:14]3[CH2:15][CH2:16][N:11]([C:6]4[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=4[O:4][CH:2]([CH3:1])[CH3:3])[CH2:12][CH2:13]3)[CH:19]=2)[C:32](=[O:31])[CH2:33]1

Participants

4

Reactant 2

HCID 778283-Methylglutaric anhydrideHCID 10521066HCID 10521066, compound

Product 1

HCID 108372254-Methyl-1-[[3-[[1-[2-(1-methylethoxy)phenyl]-4-piperazinyl]methyl]phenyl]methyl]piperidine-2,6-dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 3-[[1-[2-(1-methylethoxy)phenyl]-4-piperazinyl]methyl]benzyl amine (2.32 g, 6.84 mmol; prepared as described in Example 7), 3-methylglutaric anhydride (0.88 g, 6.84 mmol), and THF (20 mL) was stirred at room temperature for 3 h and then concentrated to an oily residue. This material was dissolved in acetic anhydride (25 mL), heated at 100° C. for 4 h, cooled, and added slowly to saturated aqueous NaHCO3. Extraction with CH2Cl2, separation of the organic layer, drying, filtration and evaporation afforded an oil. This material was chromatographed on flash grade silica using 97:3/CH2Cl2 :MeOH to give 4-methyl-1-[[3-[[1-[2-(1-methylethoxy)phenyl]-4-piperazinyl]methyl]phenyl]methyl]piperidine-2,6-dione as an oil. This was dissolved in ether and added to ethereal HCl causing a solid to form. Filtration afforded 4-methyl-1-[[3-[[ 1-[2-(1-methylethoxy)phenyl]-4-piperazinyl]methyl]phenyl]methyl]piperidine-2,6-dione dihydrochloride (1.43 g, 40%), m.p. 196°-200° C. H-1 NMR and mass spectral analysis supported the assigned structure.

Workup

  1. concentrationconcentrated to an oily residue
  2. dissolutionThis material was dissolved in acetic anhydride (25 mL)
  3. temperaturecooled
  4. additionadded slowly to saturated aqueous NaHCO3
  5. extractionExtraction
  6. customwith CH2Cl2, separation of the organic layer
  7. customdrying
  8. filtrationfiltration and evaporation
  9. customafforded an oil
  10. customThis material was chromatographed on flash grade silica using 97:3/CH2Cl2

Sources & evidence

ORD record
ord-a4839e4bebb5421abff23d53766cba7a
Source dataset
uspto-grants-1994_05
Patent number
US05314885

Reaction notes

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