N,N,N',N'-Tetramethylethylenediamine → HCID 71146962, compound

HRID 1052167Notes

Reaction equation

HRID 1052167 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])C)=[O:9])[CH2:4][CH2:3]1.CN(C)CCN(C)C.C([Li])(CC)C.[CH2:28]([N:35]1[CH2:40]CC(=O)C[CH2:36]1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.[Cl-].[NH4+]>O1CCCC1>[CH2:28]([N:35]1[CH2:40][CH2:13][C:11]2([CH:6]3[CH2:7][N:2]([CH3:1])[CH2:3][CH2:4][N:5]3[C:8](=[O:9])[O:10]2)[CH2:14][CH2:36]1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

7

Reactant 5

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 192201-Benzyl-4-piperidoneHCID 25517Ammonium ChlorideHCID 114013941-Boc-4-methylpiperazineHCID 178418400CID 53628100

Product 1

HCID 71146962HCID 71146962, compoundYield 46.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A mixture of tert-butyl 4-methylpiperazine-1-carboxylate (24.2 g), N,N,N′,N′-tetramethylethane-1,2-diamine (21 g) and tetrahydrofuran (500 mL) was cooled to −78° C. under a nitrogen atmosphere, and sec-butyllithium (184 mL, 1.3M cyclohexane solution) was added dropwise over 1.5 hr while stirring. Furthermore, the mixture was stirred at the same temperature for 2 hr, the reaction system was heated to 30° C., and the mixture was stirred for 1.5 hr. Thereafter, the reaction system was cooled again to −78° C., and a solution of 1-benzylpiperidin-4-one (28.3 g) in tetrahydrofuran (50 mL) was added dropwise over 1 hr. The reaction system was stirred at room temperature overnight, and the mixture was cooled to 0° C. Saturated aqueous ammonium chloride solution (100 mL) was added, and the mixture was stirred at room temperature for 30 min. The mixture was extracted with ethyl acetate (300 mL), and the extract was washed with water (300 mL) and dried over anhydrous sodium sulfate. Insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound (17.6 g) as a brown oil.

Workup

  1. stirringFurthermore, the mixture was stirred at the same temperature for 2 hr
  2. temperaturethe reaction system was heated to 30° C.
  3. stirringthe mixture was stirred for 1.5 hr
  4. temperatureThereafter, the reaction system was cooled again to −78° C.
  5. stirringThe reaction system was stirred at room temperature overnight
  6. temperaturethe mixture was cooled to 0° C
  7. stirringthe mixture was stirred at room temperature for 30 min
  8. extractionThe mixture was extracted with ethyl acetate (300 mL)
  9. washthe extract was washed with water (300 mL)
  10. dry with materialdried over anhydrous sodium sulfate
  11. customInsoluble material was removed by filtration
  12. concentrationthe filtrate was concentrated under reduced pressure
  13. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-1def206b499e4a658f6c338594d31ee5
Source dataset
uspto-grants-2016_07
Patent number
US09388195B2

Reaction notes

Loading…